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1. Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Author

Barrachina, Maria N., Pernes, Gerard, Becker, Isabelle C., Allaeys, Isabelle, Hirsch, Thomas I., Groeneveld, Dafna J., Khan, Abdullah O., Freire, Daniela, Guo, Karen, Carminita, Estelle, Morgan, Pooranee K., Collins, Thomas J. C., Mellett, Natalie A., Wei, Zimu, Almazni, Ibrahim, Italiano, Joseph E., Luyendyk, James, Meikle, Peter J., Puder, Mark, Morgan, Neil V., Boilard, Eric, Murphy, Andrew J., and Machlus, Kellie R.

Published
2023
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13. Thrombopoietin levels in sepsis and septic shock – a systematic review and meta-analysis.

Author

Liu, Chang, Görlich, Dennis, Lowell, Clifford A., Italiano, Joseph E., Rossaint, Jan, Bender, Markus, Zarbock, Alexander, and Margraf, Andreas

Subjects
SEPTIC shock, SEPSIS, THROMBOPOIETIN, SCIENCE databases, IMMUNOMODULATORS, IMMUNE system, DATABASE searching
Abstract

Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes. Indeed, altered platelet turnover, thrombotic events, and changes in thrombopoietin levels in systemic inflammation have been reported, but thrombopoietin-levels in sepsis and septic-shock have not yet been systematically evaluated. We therefore performed a meta-analysis of thrombopoietin (TPO)-levels in patients with sepsis. Two independent reviewers screened records and full-text articles for inclusion. Scientific databases were searched for studies examining thrombopoietin levels in adult sepsis and septic-shock patients until August 1st 2022. Of 95 items screened, six studies met the inclusion criteria, including 598 subjects. Both sepsis and severe sepsis were associated with increased levels of thrombopoietin (sepsis vs. control: standardized mean difference 3.06, 95 % CI 1.35–4.77; Z=3.50, p=0.0005) (sepsis vs. severe sepsis: standardized mean difference −1.67, 95 % CI −2.46 to −0.88; Z=4.14, p<0.0001). TPO-levels did not show significant differences between severe sepsis and septic shock patients but differed between sepsis and inflammation-associated non-septic controls. Overall, high heterogeneity and low sample size could be noted. Concluding, increased levels of thrombopoietin appear to be present both in sepsis and severe sepsis with high heterogeneity but thrombopoietin does not allow to differentiate between severe sepsis and septic-shock. TPO may potentially serve to differentiate sepsis from non-septic trauma and/or tissue damage related (systemic) inflammation. Usage of different assays and high heterogeneity demand standardization of methods and further large multicenter trials. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration

Author

Cloutier, Nathalie, Allaeys, Isabelle, Marcoux, Genevieve, Machlus, Kellie R., Mailhot, Benoit, Zufferey, Anne, Levesque, Tania, Becker, Yann, Tessandier, Nicolas, Melki, Imene, Zhi, Huiying, Poirier, Guy, Rondina, Matthew T., Italiano, Joseph E., Flamand, Louis, McKenzie, Steven E., Cote, Francine, Nieswandt, Bernhard, Khan, Waliul I., Flick, Matthew J., Newman, Peter J., Lacroix, Steve, Fortin, Paul R., and Boilard, Eric

Published
2018

19. Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4

Author

Hildick-Smith, Gordon J, Cooney, Jeffrey D, Garone, Caterina, Kremer, Laura S, Haack, Tobias B, Thon, Jonathan N, Miyata, Non, Lieber, Daniel S, Calvo, Sarah E, Akman, H Orhan, Yien, Yvette Y, Huston, Nicholas C, Branco, Diana S, Shah, Dhvanit I, Freedman, Matthew L, Koehler, Carla M, Italiano, Joseph E, Merkenschlager, Andreas, Beblo, Skadi, Strom, Tim M, Meitinger, Thomas, Freisinger, Peter, Donati, M Alice, Prokisch, Holger, Mootha, Vamsi K, DiMauro, Salvatore, and Paw, Barry H

Subjects
Hematology, Pediatric, Adolescent, Anemia, Macrocytic, Animals, Child, Erythropoiesis, Exome, Female, Gene Knockdown Techniques, Humans, Membrane Proteins, Mitochondrial Diseases, Mitochondrial Proteins, Mutation, Zebrafish, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia.

Published
2013

23. A Critical Role for ERO1α in Arterial Thrombosis and Ischemic Stroke

Author

Jha, Vishwanath, primary, Xiong, Bei, additional, Kumari, Tripti, additional, Brown, Gavriel, additional, Wang, Jinzhi, additional, Kim, Kyungho, additional, Lee, Jingu, additional, Asquith, Nathan, additional, Gallagher, John, additional, Asherman, Lillian, additional, Lambert, Taylor, additional, Bai, Yanyan, additional, Du, Xiaoping, additional, Min, Jeong-Ki, additional, Sah, Rajan, additional, Javaheri, Ali, additional, Razani, Babak, additional, Lee, Jin-Moo, additional, Italiano, Joseph E., additional, and Cho, Jaehyung, additional

Published
2023
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30. Contributors

Author

Alsousou, Joseph, primary, Angiolillo, Dominick J., additional, Arachiche, Amal, additional, Aster, Richard H., additional, Barbui, Tiziano, additional, Basili, Stefania, additional, Battinelli, Elisabeth M., additional, Bavry, Anthony A., additional, Bergmeier, Wolfgang, additional, Bertrand, Gerald, additional, Bhatt, Deepak L., additional, Blair, Thomas A., additional, Bledzka, Kamila, additional, Borst, Oliver, additional, Bouck, Emma G., additional, Brass, Lawrence F., additional, Bray, Paul F., additional, Briggs, Carol, additional, Brzoska, Tomasz, additional, Bussel, James B., additional, Cattaneo, Marco, additional, Chakravorty, Subarna, additional, Chan, Noel C., additional, Chaturvedi, Shruti, additional, Chong, Beng H., additional, Clemetson, Kenneth J., additional, Clemetson, Jeannine M., additional, Coller, Barry S., additional, del Zoppo, Gregory J., additional, Despotovic, Jenny M., additional, Diamond, Scott L., additional, Easton, J. Donald, additional, Eto, Koji, additional, Falet, Hervé, additional, Ferrer-Marin, Francisca, additional, Finazzi, Guido, additional, Flaumenhaft, Robert, additional, Freedman, Jane E., additional, Frelinger, Andrew L., additional, Freson, Kathleen, additional, Gasecka, Aleksandra, additional, Gawaz, Meinrad, additional, Giannini, Silvia, additional, Greinacher, Andreas, additional, Gremmel, Thomas, additional, Gurbel, Paul A., additional, Haining, Elizabeth J., additional, Han, Xu, additional, Harrison, Paul, additional, Hayward, Catherine P.M., additional, Hoffmeister, Karin, additional, Hvas, Anne-Mette, additional, Israels, Sara J., additional, Italiano, Joseph E., additional, Jeong, Young-Hoon, additional, Johnson, Andrew D., additional, Kaplan, Cecile, additional, Karagiannis, Peter, additional, Kato, Gregory J., additional, Kemble, Samuel, additional, Kolandaivelu, Kumaran, additional, Koupenova, Milka, additional, Kuter, David J., additional, Lambert, Michele P., additional, Lee, Robert H., additional, Levin, Jack, additional, Li, Renhao, additional, Li, Zhenyu, additional, Li, Zihai, additional, Li, Anqi, additional, Liani, Rossella, additional, Lordkipanidzé, Marie, additional, Lorenz, Viola, additional, Machlus, Kellie R., additional, Mahtta, Dhruv, additional, Mannucci, Pier Mannuccio, additional, McCrae, Keith R., additional, Metelli, Alessandra, additional, Michelson, Alan D., additional, Moffat, Karen A., additional, Moon, Jae Youn, additional, Morrissey, James H., additional, Mutch, Nicola J., additional, Nagy, Zoltan, additional, Ni, Heyu, additional, Nicolson, Phillip L.R., additional, Nieman, Marvin T., additional, Nieuwland, Rienk, additional, Onselaer, Marie-Blanche, additional, Patrono, Carlo, additional, Plow, Edward F., additional, Poncz, Mortimer, additional, Poon, Man-Chiu, additional, Poulter, Natalie S., additional, Poventud-Fuentes, Izmarie, additional, Provost, Patrick, additional, Qin, Jun, additional, Rayes, Julie, additional, Reiner, Alexander P., additional, Riesenberg, Brian, additional, Roberts, Irene A.G., additional, Rondina, Matthew T., additional, Rowley, Jesse W., additional, Santilli, Francesca, additional, Scharf, Rüdiger E., additional, Senis, Yotis A., additional, Sharda, Anish, additional, Siddon, Alexa J., additional, Siljander, Pia R.-M., additional, Tricoci, Pierluigi, additional, Simeone, Paola, additional, Smith, Stephanie A., additional, Smyth, Susan S., additional, Snyder, Edward L., additional, Sola-Visner, Martha, additional, Stalker, Timothy J., additional, Stefanini, Lucia, additional, Sugimoto, Naoshi, additional, Sundd, Prithu, additional, Tantry, Udaya S., additional, Tefferi, Ayalew, additional, Thomas, Steven G., additional, Thomas, Mark R., additional, Tomaiuolo, Maurizio, additional, Tormey, Christopher A., additional, Tsai, Han-Mou, additional, Violi, Francesco, additional, Warkentin, Theodore E., additional, Watson, Steve P., additional, Weitz, Jeffrey I., additional, Welsh, John, additional, Weyrich, Andrew S., additional, Wilcox, David A., additional, Wu, Bill X., additional, Yeaman, Michael R., additional, Zhu, Li, additional, Zimmerman, Guy A., additional, and Zunica, Elizabeth R., additional

Published
2019
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34. Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36

Author

Barrachina, Maria N, primary, Pernes, Gerard, additional, Becker, Isabelle C, additional, Allaeys, Isabelle, additional, Hirsch, Thomas I., additional, Groeneveld, Dafna J, additional, Khan, Abdullah O., additional, Freire, Daniela, additional, Guo, Karen, additional, Carminita, Estelle, additional, Morgan, Pooranee K, additional, Collins, Thomas J, additional, Mellett, Natalie A, additional, Wei, Zimu, additional, Almazni, Ibrahim, additional, Italiano, Joseph E., additional, Luyendyk, James, additional, Meikle, Peter J, additional, Puder, Mark, additional, Morgan, Neil V., additional, Boilard, Eric, additional, Murphy, Andrew J, additional, and Machlus, Kellie R, additional

Published
2023
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37. Contributors

Author

Abdel-Wahab, Omar, primary, Abrahm, Janet L., additional, Adams, Sharon, additional, Adewoye, Adeboye H., additional, Allen, Carl, additional, Ambinder, Richard F., additional, Anasetti, Claudio, additional, Anastasi, John, additional, Anderson, Julia A., additional, Antin, Joseph H., additional, Antony, Aśok C., additional, Araten, David J., additional, Armand, Philippe, additional, Armstrong, Gillian, additional, Armstrong, Scott A., additional, Arnold, Donald M., additional, Artz, Andrew S., additional, Awan, Farrukh T., additional, Baglin, Trevor P., additional, Benson, Don M., additional, Benz, Edward J., additional, Berliner, Nancy, additional, Bhagat, Govind, additional, Bhardwaj, Nina, additional, Bhatia, Ravi, additional, Bhatia, Smita, additional, Bhatt, Mihir D., additional, Bhatt, Vijaya Raj, additional, Bitan, Menachem, additional, Blinderman, Craig D., additional, Bollard, Catherine M., additional, Braun, Benjamin S., additional, Brenner, Malcolm K., additional, Brittenham, Gary M., additional, Brodsky, Robert A., additional, Brown, Myles, additional, Broxmeyer, Hal E., additional, Brummel-Ziedins, Kathleen, additional, Brunner, Andrew M., additional, Buadi, Francis K., additional, Burkhardt, Birgit, additional, Burns, Melissa, additional, Byrd, John C., additional, Caimi, Paolo F., additional, Caligiuri, Michael A., additional, Canavan, Michelle, additional, Cantor, Alan B., additional, Carcao, Manuel, additional, Carroll, Michael C., additional, Carty, Shannon A., additional, Castillo, Jorge J., additional, Chan, Anthony K.C., additional, Chapin, John, additional, Chiu, April, additional, Chute, John P., additional, Clark, David B., additional, Coates, Thomas D., additional, Cogle, Christopher R., additional, Connell, Nathan T., additional, Cooke, Elizabeth, additional, Cooley, Sarah, additional, Corradini, Paolo, additional, Creager, Mark A., additional, Creger, Richard J., additional, Cromwell, Caroline, additional, Crowther, Mark A., additional, Cushing, Melissa M., additional, Cutler, Corey, additional, Dang, Chi V., additional, Danial, Nika N., additional, Dave, Sandeep S., additional, DeCaprio, James A., additional, Dinauer, Mary C., additional, Dinner, Shira, additional, Diz-Küçükkaya, Reyhan, additional, Dodd, Roger Y., additional, Donato, Michele L., additional, Dorshkind, Kenneth, additional, Dotti, Gianpietro, additional, Dror, Yigal, additional, Dunleavy, Kieron, additional, Dvorak, Christopher C., additional, Ebert, Benjamin L., additional, Eck, Michael J., additional, Eikelboom, John W., additional, Epperla, Narendranath, additional, Ershler, William B., additional, Evans, William E., additional, Faderl, Stefan, additional, Ferrara, James L.M., additional, Filipovich, Alexandra Hult, additional, Fischer, Martin, additional, Fredenburgh, James C., additional, Friedman, Kenneth D., additional, Fuchs, Ephraim, additional, Fuller, Stephen J., additional, Gailani, David, additional, Galipeau, Jacques, additional, Gallagher, Patrick G., additional, Ganapathi, Karthik A., additional, Gardner, Lawrence B., additional, Gee, Adrian P., additional, Gerson, Stanton L., additional, Gertz, Morie A., additional, Giardina, Patricia J., additional, Gibson, Christopher J., additional, Golan, Karin, additional, Golub, Todd R., additional, Gonzales, Matthew J., additional, Gotlib, Jason, additional, Gottschalk, Stephen, additional, Grant, Marianne A., additional, Graubert, Timothy A., additional, Gregg, Xylina T., additional, Gribben, John G., additional, Gross, Dawn M., additional, Gruber, Tanja A., additional, Guitart, Joan, additional, Gurbuxani, Sandeep, additional, Gur-Cohen, Shiri, additional, Gutierrez, Alejandro, additional, Hamadani, Mehdi, additional, Hari, Parameswaran N., additional, Hartwig, John H., additional, Hayman, Suzanne R., additional, Hayward, Catherine P.M., additional, Hebbel, Robert P., additional, Heslop, Helen E., additional, Hillis, Christopher, additional, Hillyer, Christopher D., additional, Ho, Karin, additional, Hockenbery, David M., additional, Hoffman, Ronald, additional, Hogg, Kerstin E., additional, Holtan, Shernan G., additional, Horny, Hans-Peter, additional, Hsu, Yen-Michael S., additional, Hunter, Zachary R., additional, Huntington, James A., additional, Iancu-Rubin, Camelia, additional, Iqbal, Ali, additional, Isenman, David E., additional, Israels, Sara J., additional, Italiano, Joseph E., additional, Jaffe, Elaine S., additional, Jaffer, Iqbal H., additional, Jagannath, Sundar, additional, Jäger, Ulrich, additional, Jain, Nitin, additional, James, Paula, additional, Jeha, Sima, additional, Jordan, Michael B., additional, Josephson, Cassandra D., additional, Jung, Moonjung, additional, Kager, Leo, additional, Kambayashi, Taku, additional, Kanakry, Jennifer A., additional, Kantarjian, Hagop M., additional, Kaplan, Jason, additional, Karafin, Matthew S., additional, Karsan, Aly, additional, Kaufman, Randal J., additional, Kaufman, Richard M., additional, Keller, Frank G., additional, Kelly, Kara M., additional, Kessler, Craig M., additional, Key, Nigel S., additional, Keyzner, Alla, additional, Khandoga, Alexander G., additional, Khanna-Gupta, Arati, additional, Khatib-Massalha, Eman, additional, Klein, Harvey G., additional, Knoechel, Birgit, additional, Kollet, Orit, additional, Konkle, Barbara A., additional, Kontoyiannis, Dimitrios P., additional, Koreth, John, additional, Koretzky, Gary A., additional, Kotecha, Dipak, additional, Kremyanskaya, Marina, additional, Kumari, Anju, additional, Kuzel, Timothy M., additional, Küppers, Ralf, additional, Lacy, Martha Q., additional, Ladas, Elana, additional, Landier, Wendy, additional, Lapid, Kfir, additional, Lapidot, Tsvee, additional, Larson, Peter J., additional, Levi, Marcel, additional, Lewis, Russell E., additional, Liebman, Howard A., additional, Lillicrap, David, additional, Lim, Wendy, additional, Lin, Judith C., additional, Lindblad, Robert, additional, Lip, Gregory Y.H., additional, Little, Jane A., additional, Lohr, Jens G., additional, López, José A., additional, Luscinskas, Francis W., additional, Maciejewski, Jaroslaw P., additional, Majhail, Navneet S., additional, Manches, Olivier, additional, Mandle, Robert J., additional, Mann, Kenneth G., additional, Manno, Catherine S., additional, Marcogliese, Andrea N., additional, Mariani, Guglielmo, additional, Marincola, Francesco M., additional, Mascarenhas, John, additional, Massberg, Steffen, additional, McEver, Rodger P., additional, McGrath, Emer, additional, McKinney, Matthew S., additional, Mehta, Rohtesh S., additional, Mentzer, William C., additional, Merlini, Giampaolo, additional, Merryman, Reid, additional, Michel, Marc, additional, Migliaccio, Anna Rita, additional, Miller, Jeffrey S., additional, Mims, Martha P., additional, Mondoro, Traci Heath, additional, Moorehead, Paul, additional, Muniz, Luciana R., additional, Munshi, Nikhil C., additional, Najfeld, Vesna, additional, Nayak, Lalitha, additional, Nazy, Ishac, additional, Neff, Anne T., additional, Ness, Paul M., additional, Notarangelo, Luigi D., additional, O'Brien, Sarah H., additional, O'Connor, Owen A., additional, O'Donnell, Martin, additional, Olson, Amanda, additional, Orkin, Stuart H., additional, Pai, Menaka, additional, Pai, Sung-Yun, additional, Paidas, Michael, additional, Panch, Sandhya R., additional, Pande, Reena L., additional, Papayannopoulou, Thalia, additional, Parikh, Rahul, additional, Petersdorf, Effie W., additional, Peterson, Shane E., additional, Pittaluga, Stefania, additional, Ponce, Doris M., additional, Popolo, Laura, additional, Prchal, Josef T., additional, Pui, Ching-Hon, additional, Puigserver, Pere, additional, Rak, Janusz, additional, Ramos, Carlos A., additional, Rand, Jacob H., additional, Rand, Margaret L., additional, Rao, Dinesh S., additional, Ravandi, Farhad, additional, Rawlings, David J., additional, Reddy, Pavan, additional, Reding, Mark T., additional, Reiter, Andreas, additional, Rice, Lawrence, additional, Riese, Matthew J., additional, Ritchey, Arthur Kim, additional, Roberts, David J., additional, Roman, Elizabeth, additional, Rooney, Cliona M., additional, Rosen, Steven T., additional, Rosenthal, David S., additional, Rossmann, Marlies P., additional, Rot, Antal, additional, Rowley, Scott D., additional, Rubnitz, Jeffrey E., additional, Rydz, Natalia, additional, Salama, Mohamed E., additional, Sauk, Steven, additional, Saunthararajah, Yogen, additional, Savage, William, additional, Scadden, David, additional, Schaefer, Kristen G., additional, Schiffman, Fred, additional, Schneidewend, Robert, additional, Schrier, Stanley L., additional, Schuchman, Edward H., additional, Scullion, Bridget Fowler, additional, Selvaggi, Kathy J., additional, Senoo, Keitaro, additional, Shaheen, Montaser, additional, Shaz, Beth H., additional, Shelburne, Samuel A., additional, Shpall, Elizabeth J., additional, Shurin, Susan B., additional, Siegal, Deborah, additional, Silberstein, Leslie E., additional, Silberstein, Lev, additional, Silverstein, Roy L., additional, Sloan, Steven R., additional, Smith, Franklin O., additional, Smith, James W., additional, Smith, Katy, additional, Steensma, David P., additional, Steinberg, Martin H., additional, Stock, Wendy, additional, Storry, Jill R., additional, Stramer, Susan L., additional, Strauss, Ronald G., additional, Stroncek, David F., additional, Taylor, Justin, additional, Thota, Swapna, additional, Treon, Steven P., additional, Tulpule, Anil, additional, Valdes, Roberto Ferro, additional, Valent, Peter, additional, Vedantham, Suresh, additional, Vercellotti, Gregory M., additional, Verneris, Michael R., additional, Vichinsky, Elliott P., additional, von Andrian, Ulrich H., additional, Vose, Julie M., additional, Wagner, Andrew J., additional, Wang, Ena, additional, Wang, Jia-huai, additional, Warkentin, Theodore E., additional, Wasserstein, Melissa P., additional, Webster, Ann, additional, Weisdorf, Daniel J., additional, Weitz, Jeffrey I., additional, Westhoff, Connie M., additional, Wheeler, Allison P., additional, Widick, Page, additional, Wiley, James S., additional, William, Basem M., additional, Williams, David A., additional, Wilson, Wyndham H., additional, Wolfe, Joanne, additional, Wolgast, Lucia R., additional, Wood, Deborah, additional, Wu, Jennifer, additional, Yahalom, Joachim, additional, Yee, Donald L., additional, Younes, Anas, additional, Young, Neal S., additional, and Zeller, Michelle P., additional

Published
2018
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42. Platelet ERO1α Is Crucial for Ca2+ Mobilization and Platelet Activation in Atherothrombosis

Author

Jha, Vishwanath, primary, Kumari, Tripti, additional, Xiong, Bei, additional, Kim, Kyungho, additional, Wang, Jingzhi, additional, Brown, Gavriel, additional, Asquith, Nathan, additional, Gallagher, John, additional, Asherman, Lillian, additional, Bai, Yanyan, additional, Du, Xiaoping, additional, Min, Jeong-Ki, additional, Razani, Babak, additional, Italiano, Joseph E., additional, Lee, Jin-Moo, additional, and Cho, Jaehyung, additional

Published
2022
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45. Megakaryocytes compensate for Kit insufficiency in murine arthritis

Author

Cunin, Pierre, Penke, Loka R., Thon, Jonathan N., Monach, Paul A., Jones, Tatiana, Chang, Margaret H., Chen, Mary M., Melki, Imene, Lacroix, Steve, Iwakura, Yoichiro, Ware, Jerry, Gurish, Michael F., Italiano, Joseph E., Boilard, Eric, and Nigrovic, Peter A.

Subjects
Bone marrow cells -- Research, Mast cells -- Research, Arthritis -- Research, Health care industry
Abstract

The growth factor receptor Kit is involved in hematopoietic and nonhematopoietic development. Mice bearing Kit defects lack mast cells; however, strains bearing different Kit alleles exhibit diverse phenotypes. Herein, we investigated factors underlying differential sensitivity to IgG-mediated arthritis in 2 mast cell-deficient murine lines: [Kit.sup.Wsh/Wsh], which develops robust arthritis, and [Kit.sup.W/Wv], which does not. Reciprocal bone marrow transplantation between [Kit.sup.W/Wv] and [Kit.sup.Wsh/Wsh] mice revealed that arthritis resistance reflects a hematopoietic defect in addition to mast cell deficiency. In [Kit.sup.W/Wv] mice, restoration of susceptibility to IgG-mediated arthritis was neutrophil independent but required IL-1 and the platelet/ megakaryocyte markers NF-E2 and glycoprotein VI. In [Kit.sup.W/Wv] mice, platelets were present in numbers similar to those in WT animals and functionally intact, and transfer of WT platelets did not restore arthritis susceptibility. These data implicated a platelet-independent role for the megakaryocyte, a Kit-dependent lineage that is selectively deficient in [Kit.sup.W/Wv] mice. Megakaryocytes secreted IL-1 directly and as a component of circulating microparticles, which activated synovial fibroblasts in an IL-1-dependent manner. Transfer of WT but not IL-1-deficient megakaryocytes restored arthritis susceptibility to [Kit.sup.W/Wv] mice. These findings identify functional redundancy among Kit-dependent hematopoietic lineages and establish an unanticipated capacity of megakaryocytes to mediate IL-1-driven systemic inflammatory disease., Introduction Mast cells (MCs) were first described as tissue-resident cells that stain brightly with aniline dyes (1). Their highly granular appearance reflects their capacity to release a wide range of [...]

Published
2017
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