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Sepsis is a severe inflammatory condition associated with high mortality. Transmigration of neutrophils into tissues increases their lifespan to promote deleterious function. Junctional adhesion molecule‐C (JAM‐C) plays a pivotal role in neutrophil transmigration into tissues. We aim to study the role of JAM‐C on the aging of neutrophils to cause sepsis‐induced acute lung injury (ALI). Sepsis was induced in C57BL/6J mice by cecal ligation and puncture (CLP) and JAM‐C expression in serum was assessed. Bone marrow‐derived neutrophils (BMDN) were treated with recombinant mouse JAM‐C (rmJAM‐C) ex vivo and their viability was assessed. CLP‐operated animals were administrated with either isotype IgG or anti‐JAM‐C Ab at a concentration of 3 mg/kg and after 20 h, aged neutrophils (CXCR4+) were assessed in blood and lungs and correlated with systemic injury and inflammatory markers. Soluble JAM‐C level in serum was up‐regulated during sepsis. Treatment with rmJAM‐C inhibited BMDN apoptosis, thereby increasing their lifespan. CLP increased the frequencies of CXCR4+ neutrophils in blood and lungs, while treatment with anti‐JAM‐C Ab significantly reduced the frequencies of CXCR4+ aged neutrophils. Treatment with anti‐JAM‐C Ab significantly reduced systemic injury markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) as well as systemic and lung inflammatory cytokines (IL‐6 and IL‐1β) and chemokine (macrophage inflammatory protein‐2). The blockade of JAM‐C improved lung histology and reduced neutrophil contents in lungs of septic mice. Thus, reduction of the pro‐inflammatory aged neutrophils by blockade of JAM‐C has a novel therapeutic potential in sepsis‐induced ALI. Blood JAM‐C levels are increased during sepsis, causing neutrophil aging by up‐regulating surface CXCR4 expression. Blocking JAM‐C ameliorates sepsis‐induced acute lung injury in mice. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) ribonucleic acid (RNA) levels in the plasma and cerebrospinal fluid (CSF) are correlated in chronic HIV infection, but their dynamics have not been characterized during acute infection.Methods: This study analyzed predictors of CSF HIV RNA and relative degree of CNS viral transmigration expressed as plasma minus CSF HIV log10 RNA (PCratio) during untreated acute HIV infection. Cerebrospinal fluid immune markers were compared between groups with different PCratio.Results: One hundred seventeen mostly male (97%) participants in the RV254 cohort in Bangkok, Thailand, had a median age of 28 years and an estimated median 18 days duration of infection; 43 (37%) were Fiebig stages I/II. Twenty-seven (23%) had CSF HIV RNA <80 copies/mL. Those with quantifiable levels (n = 90) had median CSF HIV RNA and PCratio of 3.76 and 2.36 log10 copies/mL, respectively. Human immunodeficiency virus RNA peaked at Fiebig III in plasma and Fiebig IV in CSF. In multivariable analyses, plasma HIV RNA and CD4/CD8 ratio independently correlated with CSF HIV RNA (P < .001), whereas CD4/CD8 ratio predicted PCratio (P = .018). Participants with PCratio <1 had higher CSF neopterin, soluble (s)CD163, interleukin-6, and sCD14 levels (all P < .05).Conclusions: CD4/CD8 ratio independently correlated with CSF HIV RNA and PCratio, suggesting that immune responses modulate central nervous system viral entry at early infection. [ABSTRACT FROM AUTHOR]

The actin‐binding protein HS1 in neutrophils is required for chemokine‐induced activation of Rac1 and Rap1 supporting adhesion to endothelium and diapedesis in vivo. Neutrophil extravasation is a critical step of the innate immune system's response to inflammation. This multistep process is tightly regulated by adhesion and signaling molecules in the endothelium and neutrophils. Activation of the β2 integrin LFA‐1 is critical for adhesion of leukocytes to postcapillary venules. This step requires coordinated activation of signaling pathways in chemokine‐stimulated neutrophils, including GTPase activation and cytoskeletal remodeling, leading to conformational changes in LFA‐1. Hematopoietic cell‐specific lyn substrate 1 (HS1) is a cortactin‐related and leukocyte‐specific actin‐binding protein (ABP) that regulates several processes in various immune cells. It has been shown in vitro that HS1 is important for neutrophil chemotaxis and transendothelial migration of NK cells, but its role in neutrophil extravasation in vivo has not been investigated yet. Intravital microscopy of CXCL1‐stimulated cremaster venules revealed an increased rolling velocity and reduced neutrophil adhesion and transmigration in HS1 knockout (KO) mice. CXCL1‐induced rapid neutrophil arrest in vivo and adhesion under flow conditions in vitro were also reduced significantly. Whereas random motility of neutrophils was unaffected, chemotaxis toward a CXCL1 gradient was reduced in the absence of HS1. Further analysis of the underlying mechanisms demonstrated that HS1 controls CXCL1‐induced activation of the small GTPases Ras‐related C3 botulinum toxin substrate 1 (Rac1) and Ras‐related protein 1 (Rap1), thus supporting LFA‐1‐mediated neutrophil adhesion. Importantly, with the use of Rac1 KO neutrophils, we could show that Rac1 acts upstream of Rap1. Our results establish HS1 as an important regulator of proper Rac1 and Rap1 activation and neutrophil extravasation. [ABSTRACT FROM AUTHOR]

Stem cells possess the ability to home in and travel to damaged tissue when injected intravenously. For the cells to exert their therapeutic effect, they must cross the blood vessel wall and enter the surrounding tissues. The mechanism of extravasation injected stem cells employ for exit has yet to be characterized. Using intravital microscopy and a transgenic zebrafish line Tg(fli1a:egpf) with GFP-expressing vasculature, we documented the detailed extravasation processes in vivo for injected stem cells in comparison to white blood cells (WBCs). While WBCs left the blood vessels by the standard diapedesis process, injected cardiac and mesenchymal stem cells underwent a distinct method of extravasation that was markedly different from diapedesis. Here, the vascular wall undergoes an extensive remodeling to allow the cell to exit the lumen, while the injected cell remains distinctively passive in activity. We termed this process Angio-pello-sis, which represents an alternative mechanism of cell extravasation to the prevailing theory of diapedesis. S tem C ells 2017;35:170-180 Video Highlight: [ABSTRACT FROM AUTHOR]

ABSTRACT The aesthetic and political sides of public art have recently been examined from different theoretical vantage points. Pragmatist accounts, however, have been largely absent from the discussion. This article develops a theory of public art on some central ideas of John Dewey's aesthetics and social philosophy. From a pragmatist perspective, the best cases of public art turn out to have high social significance, for they are means of promoting the sense of community, which Dewey saw as foundational for well-functioning democracies. The Deweyan account of public art developed in this article is set against theories that explain its social value by public artworks' ability to disrupt people's everyday routines and beliefs, as well as by the political alertness they often raise. Diana Boros's recent treatment of what she calls 'visionary public art' serves as the main specimen of this approach. The Deweyan understanding of public art is illuminated and defended with the help of a reading of John Adams's On the Transmigration of Souls-a piece composed in memory of the victims of 9/11-that highlights its capacity to generate such communal experiences that have a fundamental role in Dewey's theory of democracy. [ABSTRACT FROM AUTHOR]

Benign painful and inflammatory diseases have been treated for decades with low/moderate doses of ionizing radiation ( LD- X-irradiation). Tissue macrophages regulate initiation and resolution of inflammation by the secretion of cytokines and by acting as professional phagocytes. Having these pivotal functions, we were interested in how activated macrophages are modulated by LD- X-irradiation, also with regard to radiation protection issues and carcinogenesis. We set up an ex-vivo model in which lipopolysaccharide pre-activated peritoneal macrophages (p MΦ) of radiosensitive BALB/c mice, mimicking activated macrophages under inflammatory conditions, were exposed to X-irradiation from 0·01 Gy up to 2 Gy. Afterwards, the viability of the p MΦ, their transmigration and chemotaxis, the phagocytic behaviour, the secretion of inflammatory cytokines and underlying signalling pathways were determined. Exposure of p MΦ up to a single dose of 2 Gy did not influence their viability and phagocytic function, an important fact regarding radiation protection. However, significantly reduced migration, but increased chemotaxis of p MΦ after exposure to 0·1 or 0·5 Gy, was detected. Both might relate to the resolution of inflammation. Cytokine analyses revealed that, in particular, the moderate dose of 0·5 Gy applied in low-dose radiotherapy for inflammatory diseases results in an anti-inflammatory cytokine microenvironment of p MΦ, as the secretion of the proinflammatory cytokine interleukin ( IL)-1β was reduced and that of the anti-inflammatory cytokine transforming growth factor ( TGF)-β increased. Further, the reduced secretion of IL-1β correlated with reduced nuclear translocation of nuclear factor ( NF)-κ B p65, starting at exposure of p MΦ to 0·5 Gy of X-irradiation. We conclude that inflammation is modulated by LD- X-irradiation via changing the inflammatory phenotype of macrophages. [ABSTRACT FROM AUTHOR]

Aims miR126-5p is processed from the miR126-3p/-5p duplex, which is expressed in endothelial cells and gives rise to the guide strand miR126-3p and the passenger strand miR126-5p. miR126-3p has prominent roles in vascular development and diseases, whereas the expression and physiological functions of miR126-5p are unknown. The purpose of this study was to evaluate the expression and role of miR126-5p in blood vessel endothelial cells. Methods and results miR126-5p is mostly expressed in blood vessel endothelial cells in vivo and in vitro. Gain- and loss-of-function approaches revealed that miR126-5p promotes leucocyte adhesion and represses leucocyte transendothelial migration. Two distinct target genes of miR126-5p in endothelial cells were identified: the activated leucocyte cell adhesion molecule (ALCAM) gene which codes for an adhesion molecule involved in leucocyte transendothelial migration and SetD5, a gene with previously unknown functions. Using either a blocking antibody or target protectors which specifically disrupt the miRNA/mRNA target pairing, we showed that miR126-5p promotes leucocyte adhesion by controlling the expression of SetD5 and represses transendothelial migration via the regulation of ALCAM. miR126-5p controls ALCAM and SetD5 expression in vivo in separate tissues and regulates leucocyte infiltration into inflamed lungs by repressing ALCAM expression. Conclusion miR126-5p is a functional, endothelial-enriched microRNA that participates in the control of leucocyte trafficking by regulating the expression of ALCAM and SetD5. [ABSTRACT FROM PUBLISHER]

An altered expression pattern of adhesion molecules ( AM) on the surface of immune cells is a premise for their extravasation into the central nervous system ( CNS) and the formation of acute brain lesions in multiple sclerosis ( MS). We evaluated the impact of glatiramer acetate ( GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS ( RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule ( ICAM)-1, ICAM-3, lymphocyte function-associated antigen ( LFA)-1 and very late activation antigen ( VLA)-4 were assessed in T cells ( CD3+ CD8+, CD3+ CD4+), B cells, natural killer ( NK) cells, natural killer T cells ( NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule ( PECAM)-1, P-selectin and vascular cell adhesion molecule ( VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 ( CD3+ CD4+ T cells, B cells), VLA-4 ( CD3+ CD8+ T cells, NK cells), ICAM-1 ( B cells) and ICAM-3 ( NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 ( CD3+ CD4+) and VLA-4 ( CD3+ CD4+, CD3+ CD8+, NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects. [ABSTRACT FROM AUTHOR]

Systemically administered adult mesenchymal stem cells (MSCs), which are being explored in clinical trials to treat inflammatory disease, exhibit the critical ability to extravasale at sites of inflammation. We aimed to characterize the basic cellular processes mediating this extravasation and compare them to those involved in leukocyte transmigration. Using high-resolution confocal and dynamic microscopy, we show that, like leukocytes, human bone marrow-derived MSC preferentially adhere to and migrate across tumor necrosis factor-α-activated endothelium in a vascular cell adhesion molecule-1 (VCAM-1) and G-protein-coupled receptor signaling-dependent manner. As several studies have suggested, we observed that a fraction of MSC was integrated into endothelium. In addition, we observed two modes of transmigration not previously observed for MSC: Paracellular (between endothelial cells) and transcellular (directly through individual endothelial cells) diapedesis through discrete gaps and pores in the endothelial monolayer, in association with VCAM-l-enriched "transmigratory cups". Contrasting leukocytes, MSC transmigration was not preceded by significant lateral migration and occurred on the time scale of hours rather than minutes. Interestingly, rather than lamellipodia and invadosomes, MSC exhibited nonapoptotic membrane blebbing activity that was similar to activities previously described for metastatic tumor and embryonic germ cells. Our studies suggest that low avidity binding between endothelium and MSC may grant a permissive environment for MSC blebbing. MSC blebbing was associated with early stages of transmigration, in which blebs could exert forces on underlying endothelial cells indicating potential functioning in breaching the endothelium. Collectively, our data suggest that MSC transmigrate actively into inflamed tissues via both leukocyte-like and novel mechanisms. [ABSTRACT FROM AUTHOR]

Leucocytes use sophisticated mechanisms to cross the endothelium lining the vasculature. This is initiated by chemokine- and adhesion molecule-induced intracellular signalling that controls adhesion, spreading, and motility. At the same time, adherent leucocytes trigger the endothelium, manipulating the barrier to promote their transmigration into the underlying tissues. Over the past years, our insights in the associated signalling events within the endothelium have increased considerably, albeit the order of events, their crosstalk, and the consequences for endothelial cells and leucocytes are only partially resolved. Here, we briefly review endothelial signalling that is initiated at the apical endothelial membrane, where the first contact with the leucocytes takes place and signal transduction is induced. In addition, we discuss subsequent events at endothelial cell–cell junctions insofar as they have been linked to transendothelial migration. Finally, we briefly touch upon the modulation of endothelial signalling by infectious pathogens, since these have developed additional, elegant ways to manipulate the endothelium and transendothelial migration that may provide new, relevant insights into this process. [ABSTRACT FROM PUBLISHER]

Coronary artery disease (CAD) is characterized by infiltration of monocyte derived cells in the intima of the vessel wall. We hypothesized that accumulation of these cells is caused partly by an altered monocyte transmigration process in CAD. To gain insight into this issue we applied the skin blister method that allows collection of in vivo transmigrated cells at sites of local inflammation. Nineteen patients with stable CAD and 19 matched controls were enrolled. Markers of inflammation and gradients of chemokines, as well as adhesion molecule expression and up-regulation capacity, were studied. The expression of inflammatory markers, such as C-reactive protein, interleukin (IL)-6, tumour necrosis factor-α and IL-10, was similar in patients and controls, indicating that patients were in a stable phase of the disease. Expression of adhesion molecules, CD11b and very late activation antigen-4, on peripheral monocytes did not differ between patients and controls. However, following in vivo transmigration, monocytes in patients with CAD had a significantly reduced expression and mobilization of CD11b. The effect on CD11b could not be reproduced by in vitro stimulation with blister fluid, representing a local inflammatory milieu, or in an in vitro system of transmigration. These findings point towards differences in monocyte CD11b expression and availability at an inflammatory site between patients with CAD and healthy controls. [ABSTRACT FROM AUTHOR]

The transmigration of peripheral human monocytes to the interstitium is a fundamental step in the host-defence mechanism against infections. Little is known about the state of function of in vivo transmigrated interstitial monocytes prior to differentiation into macrophages and dendritic cells. We hypothesized that newly recruited interstitial monocytes have a preserved responsiveness against bacterial-related peptides, giving them a specific role in the immediate defence against invading pathogens. In order to test this hypothesis, we explored the responsiveness of in vivo transmigrated as well as peripheral monocytes, in terms of CD11b expression and H2O2 production towards the bacterial-related peptide formylmethionylleucylphenylalanine (fMLP) by the use of a skin chamber technique. In addition, we analysed the concentration of interleukin (IL)-8, monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor (TNF)-α in the skin blister exudates and in the circulation. We demonstrate that in vivo-transmigrated monocytes had a fivefold higher CD11b expression compared to monocytes obtained from the peripheral circulation. fMLP exposure induced a significantly higher CD11b expression on transmigrated cells compared to peripheral monocytes. In addition, newly recruited monocytes had a preserved H2O2 production. The interstitial concentration of IL-8, MCP-1 and TNF-α was significantly higher in blister exudates compared to that in the peripheral circulation. Thus, in vivo transmigrated human monocytes preserve their capacity to respond towards bacterial peptides in terms of CD11b up-regulation and H2O2 generation. These data strengthen a role for newly recruited interstitial human monocytes in the immediate defence against invading pathogens. [ABSTRACT FROM AUTHOR]

The article describes a property of mature multinucleated osteoclasts to transmigrate through various cell types. By using confocal microscopy, it has been observed that multinucleated osteoclasts specifically transmigrate through confluent layers of various cell types present in the bone microenvironment in vitro.

Abstract: Continuous recruitment of neutrophils into the inflamed gastric mucosal tissue is a hallmark of Helicobacter pylori infection in humans. In this study, we examined the ability of H. pylori to induce transendothelial migration of neutrophils using a transwell system consisting of a cultured monolayer of human endothelial cells as barrier between two chambers. We showed for the first time that live H. pylori, but not formalin-killed bacteria, induced a significantly increased transendothelial migration of neutrophils. H. pylori conditioned culture medium also induced significantly increased transendothelial migration, whereas heat-inactivated culture filtrates had no effect, suggesting that the chemotactic factor was proteinaceous. Depletion of H. pylori-neutrophil activating protein (HP-NAP) from the culture filtrates resulted in significant reduction of the transmigration. Culture filtrates from isogenic HP-NAP deficient mutant bacteria also induced significantly less neutrophil migration than culture filtrates obtained from wild-type bacteria. HP-NAP did not induce endothelial cell activation, suggesting that HP-NAP acts directly on the neutrophils. In conclusion, our results demonstrate that secreted HP-NAP is one of the factors resulting in H. pylori induced neutrophil transendothelial migration. We propose that HP-NAP contributes to the continuous recruitment of neutrophils to the gastric mucosa of H. pylori infected individuals. [Copyright &y& Elsevier]

Abstract: Chlamydia pneumoniae uses blood monocytes (PBMC) for systemic dissemination, persists in atherosclerotic lesions, and has been implicated in the pathogenesis of atherosclerosis. During transmigration in a newly developed transendothelial migration model (TEM) C. pneumoniae-infected PBMC spread their infection to endothelial cells. Transmigrated PBMC retained their infectivity and transmitted the pathogen to smooth muscle cells in the lower chamber of the TEM. Detection of chlamydial HSP60 mRNA proved pathogen viability and virulence. We conclude that PBMC can spread chlamydial infection to vascular wall cells and we suggest the TEM as a novel tool to analyze host-pathogen interactions in vascular chlamydial infections. [Copyright &y& Elsevier]

The trafficking of T lymphocytes is carefully regulated by adhesive interactions with the vascular endothelium. Depending on their maturation and activation stage, T lymphocytes exhibit distinctive patterns of homing and recirculation, which is at least partly due to the selective expression of cell adhesion molecules (CAM) on the T cell surface. In order to define whether the differential usage of CAM during the steps of transendothelial migration is involved in organ-specific recirculation of different T cell subsets we compared the interaction of three different T cell populations with mouse endothelioma cell lines in vitro. Using a novel approach, where we directly compared T cell interaction with ICAM-1-deficient endothelium to wild-type endothelium, we recently demonstrated that endothelial ICAM-1 and ICAM-2 play a key role in mediating the transendothelial migration of CD4+ memory T cells. Here we show that endothelial ICAM-1 and ICAM-2 are equally required for the transendothelial migration of other T cell populations such as thymocytes and T lymphoma cells, which differ from CD4+ memory T cells in their maturation and activation stage, as well as in their surface expression of adhesion molecules. Our data therefore demonstrate that transendothelial migration of different T cell populations is mediated by the same endothelial CAM, i.e. ICAM-1 and ICAM-2, and thus subset-specific interaction of T cells with endothelial cells must be regulated prior to transendothelial migration. [ABSTRACT FROM PUBLISHER]

Discussion of buprenorphine and its potential utility for the treatment of inflammatory disorders. [ABSTRACT FROM AUTHOR]

The article presents the side of the play "Hamlet," by William Shakespeare, that shows parody of Pythagoras' metempsychosis. According to the author, Hamlet's graveyard reflection offers a parody of metempsychosis in its image of the transmigration of matter from the glorified bodies of great men to the baser forms of barrel bung and insulation caulk.

The article states that in his helpful notes to his edition of The Renaissance: Studies in Art and Poetry: The 1893 Text, Donald L. Hill offers Gautier's as a source for the "old fancy" of the transmigration and reincarnation of souls and of reminiscence of the experience of former lives', which finds famous expression in Pater's sentence, from his "Leonord" essay. Mario Praz quotes this passage in his discussion of the English development of the French idea of the book "Fatal Woman."