Search

Your search keyword '"Nourshargh S"' showing total 227 results
Start Over Author "Nourshargh S"
227 results on '"Nourshargh S"'

14. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, Zychlinsky, A, Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, and Zychlinsky, A

Abstract

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

Published
2019

15. Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study

Author

Cabrera, CP, Manson, J, Shepherd, JM, Torrance, HD, Watson, D, Longhi, MP, Hoti, M, Patel, MB, O'Dwyer, M, Nourshargh, S, Pennington, DJ, Barnes, MR, and Brohi, K

Subjects
Adult, Male, Time Factors, Critical Care and Emergency Medicine, Neutrophils, Multiple Organ Failure, Immune Cells, Immunology, Gene Expression, Pathology and Laboratory Medicine, Research and Analysis Methods, White Blood Cells, Signs and Symptoms, Spectrum Analysis Techniques, Diagnostic Medicine, Animal Cells, London, Medicine and Health Sciences, Genetics, Humans, Prospective Studies, Immune Response, Trauma Medicine, Inflammation, Blood Cells, Correction, Biology and Life Sciences, Computational Biology, Genomics, Cell Biology, Middle Aged, Genome Analysis, Flow Cytometry, Spectrophotometry, Acute Disease, Medicine, Wounds and Injuries, Multiple Organ Dysfunction Syndrome, Female, Cytophotometry, Cellular Types, Transcriptome, Transcriptome Analysis, Traumatic Injury, Blood Chemical Analysis, Research Article
Abstract

Background Severe trauma induces a widespread response of the immune system. This “genomic storm” can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. Methods and findings We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. Conclusions In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response., In a prospective cohort study, Joanna Shepherd and colleagues use whole blood transcriptome and flow cytometry analyses to identify cell populations and genes associated with a focused immune response very early after injury that develops into a widespread immune dysregulation and multiple organ dysfunction., Author summary Why was this study done? Multiple Organ Dysfunction Syndrome (MODS) is common in patients who survive critical injuries and is associated with poor patient outcomes, including death, infection, and prolonged critical care admission. MODS describes a failure of multiple organ systems (including lung, heart, kidney, and liver), and an excessive or dysfunctional immune response has been implicated in its development after trauma. The precise immune mechanisms leading to MODS are not fully understood, but the first minutes to hours after severe injury are likely to be pivotal to the development of a “normal” or “dysregulated” immune response. Our study was designed to investigate the very early immune responses to critical injury to determine whether a specific immune reaction occurs in the hyperacute timeframe that leads to widespread dysregulation and MODS. What did the researchers do and find? We studied 29,385 immune cell genes within whole blood samples obtained from 36 critically injured patients at admission (within 2 hours of injury) and compared these to samples obtained at 24 and 72 hours following injury. We analysed the differences between critically injured patient who developed MODS and those who did not and compared these to 6 patients who had minor injuries. We also used flow cytometry to analyse the numbers of circulating immune cell populations in 34 critically injured patients and compared these to healthy volunteers. Our study identified only 1,239 (4%) immune cell genes that were different between critical and control patients at admission; however, this subsequently developed into a widespread reaction by 24 hours postinjury. Comparing patients with MODS to those without MODS, we found 363 genes were different at admission, but by 24 hours postinjury, only 33 genes differentiated between the groups. Further analysis of the hyperacute timeframe demonstrated enrichment of gene pathways associated with cell death in patients with MODS and implicated neutrophils and natural killer immune cells in this response. What do these findings mean? The hyperacute timeframe is crucial to understanding the immune response to trauma and how this subsequently develops into MODS. There is a focused immune response to trauma in the hyperacute timeframe, which subsequently develops into a widespread immune reaction. The MODS signal was strongest in the hyperacute window and implicated cell death pathways and innate immune cells in this response.

Published
2017

18. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author

Cossarizza, A. (Andrea), Chang, H.-D. (Hyun-Dong), Radbruch, A. (Andreas), Andrä, I. (Immanuel), Annunziato, F. (Francesco), Bacher, P. (Petra), Barnaba, V. (Vincenzo), Battistini, L. (Luca), Bauer, W.M. (Wolfgang M.), Baumgart, S. (Sabine), Becher, B. (Burkhard), Beisker, W. (Wolfgang), Berek, C. (Claudia), Blanco, A. (Alfonso), Borsellino, G. (Giovanna), Boulais, P.E. (Philip E.), Brinkman, R.R. (Ryan R.), Büscher, M. (Martin), Busch, D.H. (Dirk), Bushnell, T.P. (Timothy P.), Cao, X. (Xuetao), Cavani, A. (Andrea), Chattopadhyay, P.K. (Pratip K.), Cheng, Q. (Qingyu), Chow, S. (Sue), Clerici, M. (Mario), Cooke, A. (Anne), Cosma, A. (Antonio), Cosmi, L. (Lorenzo), Cumano, A. (Ana), Dang, V.D. (Van Duc), Davies, D. (Derek), De Biasi, S. (Sara), Del Zotto, G. (Genny), Della Bella, S. (Silvia), Dellabona, P. (Paolo), Deniz, G. (Gunnur), Dessing, M. (Mark), Diefenbach, A. (Andreas), Santo, J.P. (James) di, Dieli, F. (Francesco), Dolf, A. (Andreas), Donnenberg, V.S. (Vera S.), Dörner, A. (Andrea), Ehrhardt, G.R.A. (Götz R. A.), Endl, E. (Elmar), Engel, P. (Pablo), Engelhardt, B. (Britta), Esser, C. (Charlotte), Everts, B. (Bart), Falk, C.S. (Christine S.), Fehniger, T.A. (Todd A.), Filby, A. (Andrew), Fillatreau, S. (Simon), Follo, M. (Marie), Förster, I. (Irmgard), Foster, J. (John), Foulds, G.A. (Gemma A.), Frenette, P.S. (Paul S.), Galbraith, D. (David), Garbi, N. (Natalio), García-Godoy, M.D. (Maria Dolores), Ghoreschi, K. (Kamran), Gibellini, L. (Lara), Goettlinger, C. (Christoph), Goodyear, C.S. (Carl), Gori, A. (Andrea), Grogan, J.L. (Jane), Gross, M. (Mor), Grützkau, A. (Andreas), Grummitt, D. (Daryl), Hahn, J. (Jonas), Hammer, Q. (Quirin), Hauser, A.E. (Anja E.), Haviland, D.L. (David L.), Hedley, D. (David), Herrera, G. (Guadalupe), Herrmann, M. (Martin), Hiepe, F. (Falk), Holland, T. (Tristan), Hombrink, P. (Pleun), Houston, J.P. (Jessica P.), Hoyer, B.F. (Bimba F.), Huang, B. (Bo), Hunter, C.A. (Christopher A.), Iannone, A. (Anna), Jäck, H.-M. (Hans-Martin), Jávega, B. (Beatriz), Jonjic, S. (Stipan), Juelke, K. (Kerstin), Jung, S. (Steffen), Kaiser, T. (Toralf), Kalina, T. (Tomas), Keller, B. (Baerbel), Khan, S. (Srijit), Kienhöfer, D. (Deborah), Kroneis, T. (Thomas), Kunkel, D. (Désirée), Kurts, C. (Christian), Kvistborg, P. (Pia), Lannigan, J. (Joanne), Lantz, O. (Olivier), Larbi, A. (Anis), LeibundGut-Landmann, S. (Salome), Leipold, M.D. (Michael D.), Levings, M.K., Litwin, V. (Virginia), Liu, Y. (Yanling), Lohoff, M. (Michael), Lombardi, G. (Giovanna), Lopez, L. (Lilly), Lovett-Racke, A. (Amy), Lubberts, E.W. (Erik), Ludewig, B. (Burkhard), Lugli, E. (Enrico), Maecker, H.T. (Holden T.), Martrus, G. (Glòria), Matarese, G. (Giuseppe), Maueröder, C. (Christian), McGrath, M. (Mairi), McInnes, I.B. (Iain), Mei, H.E. (Henrik E.), Melchers, F. (Fritz), Melzer, S. (Susanne), Mielenz, D. (Dirk), Mills, K. (Kingston), Mjösberg, J.M. (Jenny), Moore, J. (Jonni), Moran, B. (Barry), Moretta, A. (Alessandro), Moretta, L. (Lorenzo), Mosmann, T.R. (Tim R.), Müller, S. (Susann), Müller, W. (Werner), Münz, C. (Christian), Multhoff, G. (Gabriele), Munoz, L.E. (Luis Enrique), Murphy, K.M. (Kenneth M.), Nakayama, T. (Toshinori), Nasi, M. (Milena), Neudörfl, C. (Christine), Nolan, J. (John), Nourshargh, S. (Sussan), O'Connor, J.-E. (José-Enrique), Ouyang, W. (Wenjun), Oxenius, A. (Annette), Palankar, R. (Raghav), Panse, I. (Isabel), Peterson, P. (Pärt), Peth, C. (Christian), Petriz, J. (Jordi), Philips, D. (Daisy), Pickl, W. (Winfried), Piconese, S. (Silvia), Pinti, M. (Marcello), Pockley, A.G. (A. Graham), Podolska, M.J. (Malgorzata Justyna), Pucillo, C. (Carlo), Quataert, S.A. (Sally A.), Radstake, T.R.D.J. (Timothy R. D. J.), Rajwa, B. (Bartek), Rebhahn, J.A. (Jonathan A.), Recktenwald, D. (Diether), Remmerswaal, D. (Daniëlle), Rezvani, K. (Katy), Rico, L.G. (Laura G.), Robinson, J.P. (J. Paul), Romagnani, C. (Chiara), Rubartelli, A. (Anna), Ruland, J. (Jürgen), Sakaguchi, S. (Shimon), Sala-de-Oyanguren, F. (Francisco), Samstag, Y. (Yvonne), Sanderson, S. (Sharon), Sawitzki, B. (Birgit), Scheffold, A. (Alexander), Schiemann, M. (Matthias), Schildberg, F. (Frank), Schimisky, E. (Esther), Schmid, S.A. (Stephan A), Schmitt, S. (Steffen), Schober, K. (Kilian), Schüler, T. (Thomas), Schulz, A.R. (Axel Ronald), Schumacher, T.N. (Ton), Scotta, C. (Cristiano), Shankey, T.V. (T. Vincent), Shemer, A. (Anat), Simon, A.-K. (Anna-Katharina), Spidlen, J. (Josef), Stall, A.M. (Alan M.), Stark, R. (Regina), Stehle, C. (Christina), Stein, M. (Merle), Steinmetz, T. (Tobit), Stockinger, H. (Hannes), Takahama, Y. (Yousuke), Tarnok, A. (Attila), Tian, Z. (ZhiGang), Toldi, G. (Gergely), Tornack, J. (Julia), Traggiai, E. (Elisabetta), Trotter, J. (Joe), Ulrich, H. (Henning), van der Braber, M. (Marlous), Van Lier, R.A.W. (Rene A. W.), Veldhoen, M. (Marcello), Vento-Asturias, S. (Salvador), Vieira, P. (Paulo), Voehringer, D. (David), Volk, H.D. (Hans), von Volkmann, K. (Konrad), Waisman, A. (Ari), Walker, R. (Rachael), Ward, M.D. (Michael D.), Warnatz, K. (Klaus), Warth, S. (Sarah), Watson, J.V. (James V.), Watzl, C. (Carsten), Wegener, L. (Leonie), Wiedemann, A. (Annika), Wienands, J. (Jürgen), Willimsky, G. (Gerald), Wing, J. (James), Wurst, P. (Peter), Yu, L. (Liping), Yue, A. (Alice), Zhang, Q. (Qianjun), Zhao, Y. (Yi), Ziegler, S. (Susanne), Zimmermann, J. (Jakob), Cossarizza, A. (Andrea), Chang, H.-D. (Hyun-Dong), Radbruch, A. (Andreas), Andrä, I. (Immanuel), Annunziato, F. (Francesco), Bacher, P. (Petra), Barnaba, V. (Vincenzo), Battistini, L. (Luca), Bauer, W.M. (Wolfgang M.), Baumgart, S. (Sabine), Becher, B. (Burkhard), Beisker, W. (Wolfgang), Berek, C. (Claudia), Blanco, A. (Alfonso), Borsellino, G. (Giovanna), Boulais, P.E. (Philip E.), Brinkman, R.R. (Ryan R.), Büscher, M. (Martin), Busch, D.H. (Dirk), Bushnell, T.P. (Timothy P.), Cao, X. (Xuetao), Cavani, A. (Andrea), Chattopadhyay, P.K. (Pratip K.), Cheng, Q. (Qingyu), Chow, S. (Sue), Clerici, M. (Mario), Cooke, A. (Anne), Cosma, A. (Antonio), Cosmi, L. (Lorenzo), Cumano, A. (Ana), Dang, V.D. (Van Duc), Davies, D. (Derek), De Biasi, S. (Sara), Del Zotto, G. (Genny), Della Bella, S. (Silvia), Dellabona, P. (Paolo), Deniz, G. (Gunnur), Dessing, M. (Mark), Diefenbach, A. (Andreas), Santo, J.P. (James) di, Dieli, F. (Francesco), Dolf, A. (Andreas), Donnenberg, V.S. (Vera S.), Dörner, A. (Andrea), Ehrhardt, G.R.A. (Götz R. A.), Endl, E. (Elmar), Engel, P. (Pablo), Engelhardt, B. (Britta), Esser, C. (Charlotte), Everts, B. (Bart), Falk, C.S. (Christine S.), Fehniger, T.A. (Todd A.), Filby, A. (Andrew), Fillatreau, S. (Simon), Follo, M. (Marie), Förster, I. (Irmgard), Foster, J. (John), Foulds, G.A. (Gemma A.), Frenette, P.S. (Paul S.), Galbraith, D. (David), Garbi, N. (Natalio), García-Godoy, M.D. (Maria Dolores), Ghoreschi, K. (Kamran), Gibellini, L. (Lara), Goettlinger, C. (Christoph), Goodyear, C.S. (Carl), Gori, A. (Andrea), Grogan, J.L. (Jane), Gross, M. (Mor), Grützkau, A. (Andreas), Grummitt, D. (Daryl), Hahn, J. (Jonas), Hammer, Q. (Quirin), Hauser, A.E. (Anja E.), Haviland, D.L. (David L.), Hedley, D. (David), Herrera, G. (Guadalupe), Herrmann, M. (Martin), Hiepe, F. (Falk), Holland, T. (Tristan), Hombrink, P. (Pleun), Houston, J.P. (Jessica P.), Hoyer, B.F. (Bimba F.), Huang, B. (Bo), Hunter, C.A. (Christopher A.), Iannone, A. (Anna), Jäck, H.-M. (Hans-Martin), Jávega, B. (Beatriz), Jonjic, S. (Stipan), Juelke, K. (Kerstin), Jung, S. (Steffen), Kaiser, T. (Toralf), Kalina, T. (Tomas), Keller, B. (Baerbel), Khan, S. (Srijit), Kienhöfer, D. (Deborah), Kroneis, T. (Thomas), Kunkel, D. (Désirée), Kurts, C. (Christian), Kvistborg, P. (Pia), Lannigan, J. (Joanne), Lantz, O. (Olivier), Larbi, A. (Anis), LeibundGut-Landmann, S. (Salome), Leipold, M.D. (Michael D.), Levings, M.K., Litwin, V. (Virginia), Liu, Y. (Yanling), Lohoff, M. (Michael), Lombardi, G. (Giovanna), Lopez, L. (Lilly), Lovett-Racke, A. (Amy), Lubberts, E.W. (Erik), Ludewig, B. (Burkhard), Lugli, E. (Enrico), Maecker, H.T. (Holden T.), Martrus, G. (Glòria), Matarese, G. (Giuseppe), Maueröder, C. (Christian), McGrath, M. (Mairi), McInnes, I.B. (Iain), Mei, H.E. (Henrik E.), Melchers, F. (Fritz), Melzer, S. (Susanne), Mielenz, D. (Dirk), Mills, K. (Kingston), Mjösberg, J.M. (Jenny), Moore, J. (Jonni), Moran, B. (Barry), Moretta, A. (Alessandro), Moretta, L. (Lorenzo), Mosmann, T.R. (Tim R.), Müller, S. (Susann), Müller, W. (Werner), Münz, C. (Christian), Multhoff, G. (Gabriele), Munoz, L.E. (Luis Enrique), Murphy, K.M. (Kenneth M.), Nakayama, T. (Toshinori), Nasi, M. (Milena), Neudörfl, C. (Christine), Nolan, J. (John), Nourshargh, S. (Sussan), O'Connor, J.-E. (José-Enrique), Ouyang, W. (Wenjun), Oxenius, A. (Annette), Palankar, R. (Raghav), Panse, I. (Isabel), Peterson, P. (Pärt), Peth, C. (Christian), Petriz, J. (Jordi), Philips, D. (Daisy), Pickl, W. (Winfried), Piconese, S. (Silvia), Pinti, M. (Marcello), Pockley, A.G. (A. Graham), Podolska, M.J. (Malgorzata Justyna), Pucillo, C. (Carlo), Quataert, S.A. (Sally A.), Radstake, T.R.D.J. (Timothy R. D. J.), Rajwa, B. (Bartek), Rebhahn, J.A. (Jonathan A.), Recktenwald, D. (Diether), Remmerswaal, D. (Daniëlle), Rezvani, K. (Katy), Rico, L.G. (Laura G.), Robinson, J.P. (J. Paul), Romagnani, C. (Chiara), Rubartelli, A. (Anna), Ruland, J. (Jürgen), Sakaguchi, S. (Shimon), Sala-de-Oyanguren, F. (Francisco), Samstag, Y. (Yvonne), Sanderson, S. (Sharon), Sawitzki, B. (Birgit), Scheffold, A. (Alexander), Schiemann, M. (Matthias), Schildberg, F. (Frank), Schimisky, E. (Esther), Schmid, S.A. (Stephan A), Schmitt, S. (Steffen), Schober, K. (Kilian), Schüler, T. (Thomas), Schulz, A.R. (Axel Ronald), Schumacher, T.N. (Ton), Scotta, C. (Cristiano), Shankey, T.V. (T. Vincent), Shemer, A. (Anat), Simon, A.-K. (Anna-Katharina), Spidlen, J. (Josef), Stall, A.M. (Alan M.), Stark, R. (Regina), Stehle, C. (Christina), Stein, M. (Merle), Steinmetz, T. (Tobit), Stockinger, H. (Hannes), Takahama, Y. (Yousuke), Tarnok, A. (Attila), Tian, Z. (ZhiGang), Toldi, G. (Gergely), Tornack, J. (Julia), Traggiai, E. (Elisabetta), Trotter, J. (Joe), Ulrich, H. (Henning), van der Braber, M. (Marlous), Van Lier, R.A.W. (Rene A. W.), Veldhoen, M. (Marcello), Vento-Asturias, S. (Salvador), Vieira, P. (Paulo), Voehringer, D. (David), Volk, H.D. (Hans), von Volkmann, K. (Konrad), Waisman, A. (Ari), Walker, R. (Rachael), Ward, M.D. (Michael D.), Warnatz, K. (Klaus), Warth, S. (Sarah), Watson, J.V. (James V.), Watzl, C. (Carsten), Wegener, L. (Leonie), Wiedemann, A. (Annika), Wienands, J. (Jürgen), Willimsky, G. (Gerald), Wing, J. (James), Wurst, P. (Peter), Yu, L. (Liping), Yue, A. (Alice), Zhang, Q. (Qianjun), Zhao, Y. (Yi), Ziegler, S. (Susanne), and Zimmermann, J. (Jakob)

Published
2017
Full Text
View/download PDF

20. IL-1 is a potent inducer of eosinophil accumulation in rat skin. Inhibition of response by a platelet-activating factor antagonist and an anti-human IL-8 antibody

Author

Maria Jesus Sanz, Weg, V. B., Bolanowski, M. A., and Nourshargh, S.

Subjects
Immunology, Immunology and Allergy
Abstract

The aim of the present study was to investigate directly and characterize the ability of IL-1 beta in inducing eosinophil accumulation in vivo. For this purpose, we studied the recruitment of 111In-labeled eosinophils in rat skin in response to intradermally injected rat rIL-1 beta. Rat rIL-1 induced a dose-dependent accumulation of 111In-labeled eosinophils, with the maximal response being detected at 5 x 10(-13) mol/site. This response was slow in onset, progressively increasing over the 4-h period investigated. Rat rIL-1 also induced a small level of edema, as measured by the local accumulation of i.v. 125I-labeled albumin, which developed with a time course similar to that of 111In-labeled eosinophil accumulation. Co-administration of the cytokine with the IL-1R antagonist, IL-1ra, or actinomycin D, significantly inhibited the 111In-labeled eosinophil accumulation, and reduced the edema formation, induced by rat rIL-1. In addition, the 111In-labeled eosinophil accumulation was significantly suppressed in animals treated with the PAF antagonist UK-74,505 or an anti-human IL-8 mAb DM/C7. These observations demonstrate for the first time that IL-1 beta is a potent inducer of eosinophil accumulation in vivo. Moreover, the results reveal that this activity of IL-1 beta is receptor mediated and dependent on the induction of proteins that may be involved in the local generation of secondary inflammatory mediators including PAF and an IL-8-like molecule. These findings are consistent with the view that endogenously generated IL-1 may play an important role in the recruitment of eosinophils at sites of allergic inflammation.

Published
1995
Full Text
View/download PDF

21. Shed syndecan-2 inhibits angiogenesis

Author

McKay, TR, De Rossi, G, Evans, AR, Kay, E, Woodfin, A, Nourshargh, S, Whiteford, JR, McKay, TR, De Rossi, G, Evans, AR, Kay, E, Woodfin, A, Nourshargh, S, and Whiteford, JR

Abstract

Angiogenesis is essential for the development of a normal vasculature, tissue repair and reproduction, and also has roles in the progression of diseases such as cancer and rheumatoid arthritis. The heparan sulphate proteoglycan syndecan-2 is expressed on mesenchymal cells in the vasculature and, like the other members of its family, can be shed from the cell surface resulting in the release of its extracellular core protein. The purpose of this study was to establish whether shed syndecan-2 affects angiogenesis. We demonstrate that shed syndecan-2 regulates angiogenesis by inhibiting endothelial cell migration in human and rodent models and, as a result, reduces tumour growth. Furthermore, our findings show that these effects are mediated by the protein tyrosine phosphatase receptor CD148 (also known as PTPRJ) and this interaction corresponds with a decrease in active beta1 integrin. Collectively, these data demonstrate an unexplored pathway for the regulation of new blood vessel formation and identify syndecan-2 as a therapeutic target in pathologies characterised by angiogenesis.

Published
2014

22. Divergent mechanisms of action of the inflammatory cytokines interleukin 1-β and tumour necrosis factor-α in mouse cremasteric venules

Author

Young, R E, Thompson, R D, and Nourshargh, S

Subjects
Inflammation, Male, Tumor Necrosis Factor-alpha, Receptors, Leukotriene B4, Receptors, Cell Surface, Platelet Membrane Glycoproteins, Receptors, G-Protein-Coupled, Mice, Inbred C57BL, Mice, Venules, Cell Movement, Papers, Testis, Leukocytes, Animals, Cytokines, Interleukin-1
Abstract

1. Protein synthesis dependency and the role of endogenously generated platelet activating factor (PAF) and leukotriene B(4) (LTB(4)) in leukocyte migration through interleukin-1beta (IL-1beta)- and tumour necrosis factor-alpha (TNFalpha)-stimulated mouse cremasteric venules was investigated using established pharmacological interventions and the technique of intravital microscopy. 2. Based on previously obtained dose-response data, 30 ng rmIL-1beta and 300 ng rmTNFalpha were injected intrascrotally (4 h test period) to induce comparable levels of leukocyte firm adhesion and transmigration in mouse cremasteric venules. 3. Co-injection of the mRNA synthesis inhibitor, actinomycin D (0.2 mg kg(-1)), with the cytokines significantly inhibited firm adhesion (49+/-13.6%) and transmigration (67.2+/-4.2%) induced by IL-1beta, but not TNFalpha. 4. In vitro, TNFalpha (1-100 ng ml(-1)), but not IL-1beta, stimulated L-selectin shedding and increased beta(2) integrin expression on mouse neutrophils, as quantified by flow cytometry. 5. The PAF receptor antagonist, UK-74,505 (modipafant, 0.5 mg kg(-1), i.v.), had no effect on adhesion induced by either cytokine, but significantly inhibited transmigration induced by IL-1beta (66.5+/-4.5%). 6. The LTB(4) receptor antagonist, CP-105,696 (100 mg kg(-1), p.o.), significantly inhibited both IL-1beta induced adhesion (81.4+/-15.2%) and transmigration (58.7+/-7.2%), but had no effect on responses elicited by TNFalpha. Combined administration of the two antagonists had no enhanced inhibitory effects on responses induced by either cytokine. 7. The data indicate that firm adhesion and transmigration in mouse cremasteric venules stimulated by IL-1beta, but not TNFalpha, is protein synthesis dependent and mediated by endogenous generation of PAF and LTB(4). Additionally, TNFalpha but not IL-1beta, can directly stimulate mouse neutrophils in vitro. The findings provide further evidence to suggest divergent mechanisms of actions of IL-1beta and TNFalpha, two cytokines often considered to act via common molecular/cellular pathways.

Published
2002

23. CD97 antibody depletes granulocytes in mice under conditions of acute inflammation via a Fc receptor-dependent mechanism.

Author

Veninga, H., Groot, D.M. de, McCloskey, N., Owens, B.M., Dessing, M.C., Verbeek, J.S., Nourshargh, S., Eenennaam, H. van, Boots, A.M.H., Hamann, J., Veninga, H., Groot, D.M. de, McCloskey, N., Owens, B.M., Dessing, M.C., Verbeek, J.S., Nourshargh, S., Eenennaam, H. van, Boots, A.M.H., and Hamann, J.

Abstract

01 maart 2011, Item does not contain fulltext, Antibodies to the pan-leukocyte adhesion-GPCR CD97 efficiently block neutrophil recruitment in mice, thereby reducing antibacterial host defense, inflammatory disease, and hematopoietic stem cell mobilization. Here, we investigated the working mechanism of the CD97 antibody 1B2. Applying sterile models of inflammation, intravital microscopy, and mice deficient for the CD97L CD55, the complement component C3, or the FcR common gamma-chain, we show that 1B2 acts in vivo independent of ligand-binding interference by depleting PMN granulocytes in bone marrow and blood. Granulocyte depletion with 1B2 involved FcR but not complement activation and was associated with increased serum levels of TNF and other proinflammatory cytokines. Notably, depletion of granulocytes by CD97 antibody required acute inflammation, suggesting a mechanism of conditional, antibody-mediated granulocytopenia.

Published
2011

24. Tumor necrosis factor alpha-induced eosinophil accumulation in rat skin is dependent on alpha4 integrin/vascular cell adhesion molecule-1 adhesion pathways

Author

Maria Jesus Sanz, Hartnell A, Chisholm P, Williams C, Davies D, Vb, Weg, Feldmann M, Ma, Bolanowski, Rr, Lobb, and Nourshargh S

Subjects
Eosinophils, Rats, Sprague-Dawley, Antigens, CD, Tumor Necrosis Factor-alpha, Integrin alpha4, Receptors, Lymphocyte Homing, Animals, Humans, Vascular Cell Adhesion Molecule-1, Rats, Signal Transduction, Skin
Abstract

Tumor necrosis factor alpha (TNFalpha) is a cytokine implicated in the pathogenesis of numerous chronic and acute inflammatory conditions. In the present study, we have characterized the ability of TNFalpha in inducing eosinophil accumulation in rat skin and have shown the inhibitory effects of anti-alpha4 integrin and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies on this response. The intradermal injection of recombinant human TNFalpha induced a slowly developing, dose-dependent accumulation of 111In-eosinophils in rat skin that was maximal at the dose of 10(-11) mol/site. Coadministration of TNFalpha with the soluble TNFalpha receptor (p55)-IgG fusion protein (TNFR-IgG) totally inhibited the 111In-eosinophil accumulation induced by the cytokine. The TNFalpha-induced 111In-eosinophil accumulation was not affected after pretreatment of rats with the platelet-activating factor (PAF) receptor antagonist UK-74,505 or the antihuman interleukin-8 monoclonal antibody (MoAb) DM/C7. In contrast, the intravenous administration of an anti-alpha4 integrin MoAb, HP2/1 (3.5 mg/kg), or an anti-VCAM-1 MoAb, 5F10 (2 mg/kg), greatly inhibited the 111In-eosinophil accumulation induced by TNFalpha (the responses detected at 10(-11) mol/site were inhibited by 78% and 50%, respectively). These results show that TNFalpha is an effective inducer of eosinophil accumulation in vivo, with this response being dependent on an interaction between alpha4 integrins and VCAM-1.

Published
1997

27. The accumulation of 111In-eosinophils induced by inflammatory mediators, in vivo

Author

Faccioli, L H, Nourshargh, S, Moqbel, R, Williams, F M, Sehmi, R, Kay, A B, and Williams, T J

Subjects
Guinea Pigs, Indium Radioisotopes, Zymosan, Complement C5a, respiratory system, Leukotriene B4, Recombinant Proteins, Dermatitis, Atopic, Eosinophils, Cell Movement, Albumins, Animals, Female, Platelet Activating Factor, Research Article, Skin
Abstract

Eosinophils are implicated in the pathogenesis of a variety of allergic inflammatory diseases such as asthma. Several substances have been shown to be chemotactic for eosinophils in vitro, but the inflammatory mediators involved in the accumulation of eosinophils in vivo are as yet unidentified. In this study we have developed a system to measure the accumulation of 111In-eosinophils in guinea-pig skin in vivo. Horse serum-induced guinea-pig peritoneal eosinophils were radiolabelled with 111In and injected intravenously into recipient animals. 125I-albumin was also injected intravenously in order to measure local oedema formation simultaneously. A range of putative mediators was injected intradermally and responses measured for up to 2 hr. Of the mediators tested, guinea-pig C5a des Arg in zymosan-activated plasma was the most active. Recombinant human C5a (rHC5a) was also highly active, but less than the guinea-pig material. C5a des Arg in maximally activated plasma induced a 1500% increase in eosinophil accumulation, while rHC5a (10(-10) mol dose) induced a 600% increase. Platelet-activating factor (PAF) and leukotriene B4 (LTB4) were also tested for comparison. With respect to 111In-eosinophil accumulation, the order of potency of the mediators tested was as follows: guinea-pig C5a des Arg greater than LTB4 greater than PAF. In contrast, the order of potency of the mediators with respect to oedema formation was: PAF greater than guinea-pig C5a des Arg greater than LTB4. The techniques described will facilitate analysis of the mechanisms involved in eosinophil accumulation in defined inflammatory reactions.

Published
1991

28. Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo

Author

Tharp, William G, primary, Yadav, R, additional, Irimia, D, additional, Upadhyaya, A, additional, Samadani, A, additional, Hurtado, O, additional, Liu, S Y, additional, Munisamy, S, additional, Brainard, D M, additional, Mahon, M J, additional, Nourshargh, S, additional, van Oudenaarden, A, additional, Toner, M G, additional, and Poznansky, Mark C, additional

Published
2005
Full Text
View/download PDF

43. Comparative responses of human and rabbit interleukin-1 <em>in vivo</em>: effect of a recombinant interleukin-1 receptor antagonist.

Author

von Uexküll, C., Nourshargh, S., and Williams, T. J.

Subjects
*INTERLEUKIN-1, *BLOOD proteins, *CYTOKINES, *AMINO acids, *ACTINOMYCIN, *CHEMICAL inhibitors
Abstract

The ability of recombinant human and rabbit interleukin-lα (IL-lα) in inducing inflammatory responses in rabbit skin were compared. Intradermal (i.d) injections of recombinant human IL-lα and recombinant rabbit IL-lα induced intense accumulation of "In-labeled neutrophils which was dependent on the dose of the cytokines administered. Both forms of IL-1α induced very small levels of plasma protein leakage. Co-injection of the cytokines with the mRNA synthesis inhibitor actinomycin D (Act D) attenuated the number of neutrophils accumulating in response to both human and rabbit forms of IL-lα. Local injection of a recombinant human IL-1 receptor antagonist (IL-1Ra) caused a dose-dependent inhibition of local inflammatory responses initiated by human and rabbit IL-1β as well as rabbit IL-l indicating the species cross-reactivity of the antagonist. IL-1α as was selective for IL-1β in rabbit skin, as responses induced by C5adesArg and formyl-methionyl-leucyl-phenylalanine (FMLP) were not inhibited. IL-1Ra significantly inhibited the IL-1-induced neutrophil accumulation only when co-injected with the cytokine. The local administration of the antagonist 30 mm after rabbit IL- lα failed to inhibit the inflammatory response. These results suggest that the in vivo events leading to the accumulation of neutrophils in response to IL-lα are rapidly initiated. [ABSTRACT FROM AUTHOR]

Published
1992

44. The accumulation of 111In-eosinophils induced by inflammatory mediators, <em>in vivo</em>.

Author

Faccioli, L. H., Nourshargh, S., Moqbel, R., Williams, F. M., Sehmi, R., Kay, A. B., and Williams, T. J.

Subjects
*EOSINOPHILS, *BLOOD plasma, *LEUCOCYTES, *INFLAMMATORY mediators, *ALBUMINS, *PLATELET activating factor, *PHOSPHOLIPIDS
Abstract

Eosinophils are implicated in the pathogenesis of a variety of allergic inflammatory diseases such as asthma. Several substances have been shown to be chemotactic for eosinophils in vitro, but the inflammatory mediators involved in the accumulation of eosinophils in vivo are as yet unidentified. In this study we have developed a system to measure the accumulation of 111In-eosinophils in guinea-pig skin in vivo. Horse serum-induced guinea-pig peritoneal eosinophils were radiolabelled with 111In and injected intravenously into recipient animals. 125I-albumin was also injected intravenously in order to measure local oedema formation simultaneously. A range of putative mediators was injected intradermally and responses measured for up to 2 hr. Of the mediators tested, guinea-pig C5a des Arg in zymosan-activated plasma was the most active. Recombinant human C5a (rHC5a) was also highly active, but less so than the guinea-pig material. C5a des Arg in maximally activated plasma induced a 1500% increase in eosinophil accumulation, while rhC5a (10-10mol dose) induced a 600% increase. Platelet-activating factor (PAF) and leukotriene B4 (LTB4) were also tested for comparison. With respect to 111In-eosinophil accumulation, the order of potency of the mediators tested was as follows: guinea-pig C5a des Arg > LTB4> PAF. In contrast, the order of potency of the mediators with respect to oedema formation was: PAF > guinea-pig C5a des Arg> LTB4. The techniques described will facilitate analysis of the mechanisms involved in eosinophil accumulation in defined inflammatory reactions. [ABSTRACT FROM AUTHOR]

Published
1991

46. Lung eosinophilia is dependent on IL-5 and the adhesion molecules CD18 and VLA-4, in a guinea-pig model.

Author

Das, A. M., Williams, T. J., Lobb, R., and Nourshargh, S.

Subjects
EOSINOPHILS, CELL adhesion molecules, LUNG disease diagnosis, SEPHADEX, INTERLEUKIN-1
Abstract

Blood and tissue eosinophilia is a characteristic feature of a number of disease states. In experimental animals, the intravenous injection of parasitic larvae induces a profound eosinophilia that can be mimicked by the intravenous injection of Sephadex particles. In the present study, this procedure was used to investigate the mechanisms involved in the development of lung eosinophilia in a guinea-pig model. Intravenous administration of Sephadex particles to guinea-pigs resulted in a significant increase in the influx of eosinophils in the airways and in lung tissue eosinophil peroxidase (EPO) activity (at t = 24 hr). An anti-interleukin-5 (IL-5) monoclonal antibody (mAb) totally inhibited the eosinophilia in the airways and significantly reduced the lung tissue EPO activity. The concomitant accumulation of neutrophils and mononuclear cells, however, was not affected by this treatment. Monoclonal antibodies to VLA-4 and CD18 caused 58% and 62% suppression of eosinophilia in the bronchoalveolar lavage (BAL), respectively, whilst having no effect on lung tissue EPO activity. Co-administration of the two mAb resulted in total inhibition of eosinophil accumulation into BAL and significant suppression of lung tissue EPO activity (55% inhibition). This procedure also resulted in 72% inhibition of mononuclear cell influx and 68% inhibition of neutrophil influx in the BAL, the latter effect being entirely due to the actions of the anti-CD 18 mAb. The results of this study indicate for the first time a requirement for IL-5 in the development of lung eosinophilia in this model. Further, it is clear that both the molecules VLA-4 and CD18 contribute to the development of this response and that maximal inhibition of lung eosinophilia is achieved only when the two adhesion pathways are simultaneously blocked. [ABSTRACT FROM AUTHOR]

Published
1995

47. LPS-induced 111In-eosinophil accumulation in guinea-pig skin: evidence for a role for TNF-α.

Author

Weg, V. B., Walsh, D. T., Faccioli, L. H., Williams, T. J., Feldmann, M., and Nourshargh, S.

Subjects
ENDOTOXINS, GRAM-negative bacteria, NEUTROPHILS, EOSINOPHILS, PROTEINS, ACTINOMYCIN
Abstract

Lipopolysaccharide (LPS) is a major component of the cell wall of Gram-negative bacteria with powerful pro-inflammatory activities. Although the mechanisms involved in LPS-induced neutrophil accumulation have been studied extensively, few reports have focused on the effects of LPS on eosinophil infiltration. In this study we have used an in vivo model of local 111In- eosinophil accumulation in the guinea-pig to investigate the mechanisms of LPS-induced eosinophilia. Using a 4-hr in vivo test period, the intradermal injection of LPS (50-1000 ng/site) led to a marked and dose-dependent accumulation of 111In-eosinophils into guinea-pig skin sites. Time-course experiments revealed that this cell infiltration was delayed in onset, becoming significant I hr after the intradermal administration of LPS. The slow development of the response and its sensitivity to the locally administered protein synthesis inhibitor, actinomycin D, suggested that the Lis-induced 111In-eosinophil accumulation in vivo is mediated by the generation of de novo proteins. The intravenous pretreatment of guinea-pigs with a soluble turnout necrosis factor- α (TNF-α) receptor fusion protein (TNFR-IgG, 1 mg/kg), potently inhibited the 111In-eosinophil accumulation induced by LPS. Our results demonstrate that LIS can induce 111In-eosinophil accumulation in vivo in guinea-pig skin, and that this process is mediated by TNF-α. [ABSTRACT FROM AUTHOR]

Published
1995

48. Neutrophil chemorepulsion in defined interleukin‐8 gradients in vitro and in vivo

Author

Tharp, William G., Yadav, R., Irimia, D., Upadhyaya, A., Samadani, A., Hurtado, O., Liu, S‐Y., Munisamy, S., Brainard, D. M., Mahon, M. J., Nourshargh, S., Oudenaarden, A., Toner, M. G., and Poznansky, Mark C.

Abstract

We report for the first time that primary human neutrophils can undergo persistent, directionally biased movement away from a chemokine in vitro and in vivo, termed chemorepulsion or fugetaxis. Robust neutrophil chemorepulsion in microfluidic gradients of interleukin‐8 (IL‐8; CXC chemokine ligand 8) was dependent on the absolute concentration of chemokine, CXC chemokine receptor 2 (CXCR2), and was associated with polarization of cytoskeletal elements and signaling molecules involved in chemotaxis and leading edge formation. Like chemoattraction, chemorepulsion was pertussis toxin‐sensitive and dependent on phosphoinositide‐3 kinase, RhoGTPases, and associated proteins. Perturbation of neutrophil intracytoplasmic cyclic adenosine monophosphate concentrations and the activity of protein kinase C isoforms modulated directional bias and persistence of motility and could convert a chemorepellent to a chemoattractant response. Neutrophil chemorepulsion to an IL‐8 ortholog was also demonstrated and quantified in a rat model of inflammation. The finding that neutrophils undergo chemorepulsion in response to continuous chemokine gradients expands the paradigm by which neutrophil migration is understood and may reveal a novel approach to our understanding of the homeostatic regulation of inflammation.

Published
2006
Full Text
View/download PDF

50. IL-4-induced eosinophil accumulation in rat skin is dependent on endogenous TNF-alpha and alpha 4 integrin/VCAM-1 adhesion pathways

Author

Maria Jesus Sanz, Marinova-Mutafchieva L, Green P, Rr, Lobb, Feldmann M, and Nourshargh S

Subjects
Male, Time Factors, Injections, Intradermal, Tumor Necrosis Factor-alpha, Integrin alpha4, Recombinant Fusion Proteins, Indium Radioisotopes, Dose-Response Relationship, Immunologic, Antibodies, Monoclonal, Vascular Cell Adhesion Molecule-1, Intercellular Adhesion Molecule-1, Receptors, Tumor Necrosis Factor, Rats, Eosinophils, Rats, Sprague-Dawley, Solubility, Antigens, CD, Cell Movement, Receptors, Tumor Necrosis Factor, Type I, CD18 Antigens, Immunoglobulin G, Cell Adhesion, Animals, Interleukin-4, Skin
Abstract

IL-4 has been implicated in the pathogenesis of a number of allergic inflammatory disease states where the accumulation of eosinophils is a prominent feature. The aim of the present study was to use an isotopic in vivo model to investigate the ability of recombinant rat IL-4 in inducing eosinophil accumulation in rat skin. 111In-eosinophil accumulation in response to intradermally injected IL-4 was measured during 0 to 4 h, 24 to 28 h, and 48 to 52 h. Accumulation was detected during the first two periods, but not at the later time point. The accumulation during 24 to 28 h, which was dose dependent, was investigated in detail. Administration i.v. of an anti-rat VCAM-1 mAb, but not an anti-rat ICAM-1 mAb, inhibited the accumulation of 111In-eosinophils induced by IL-4 (maximum inhibition, 80%). Further, when the 111In-eosinophils were pretreated in vitro with an anti-beta 2 integrin mAb, an anti-alpha 4 integrin mAb, or a combination of both mAbs, before their injection into recipient rats, the IL-4-induced cell accumulation was inhibited by 63, 60, and 74%, respectively. Finally, coadministration of IL-4 with the soluble TNF receptor (p55)-IgG fusion protein significantly reduced the 111In-eosinophil accumulation induced by the cytokine, and TNF-alpha was detected in IL-4-injected skin sites by both immunostaining and bioassay. Our results demonstrate that IL-4 is a potent inducer of eosinophil accumulation in vivo, the response being dependent on the endogenous generation of TNF-alpha, beta 2 integrins, and alpha 4 integrin/VCAM-1 interactions.

Catalog

Books, media, physical & digital resources
See catalog results