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Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1

Woodfin, Abigail
Voisin, Mathieu-Benoit
Dejana, Elisabetta
Engelhardt, Britta
Nourshargh, Sussan
Published in Blood. 2009, vol. 113, no. 24, p. 6246-57
Abstract Leukocyte transmigration is mediated by endothelial cell (EC) junctional molecules, but the associated mechanisms remain unclear. Here we investigate how intercellular adhesion molecule-2 (ICAM-2), junctional adhesion molecule-A (JAM-A), and platelet endothelial cell adhesion molecule (PECAM-1) mediate neutrophil transmigration in a stimulus-dependent manner (eg, as induced by interleukin-1beta [IL-1beta] but not tumor necrosis factor-alpha [TNF-alpha]), and demonstrate their ability to act in sequence. Using a cell-transfer technique, transmigration responses of wild-type and TNF-alpha p55/p75 receptor-deficient leukocytes (TNFR(-/-)) through mouse cremasteric venules were quantified by fluorescence intravital microscopy. Whereas wild-type leukocytes showed a normal transmigration response to TNF-alpha in ICAM-2(-/-), JAM-A(-/-), and PECAM-1(-/-) recipient mice, TNFR(-/-) leukocytes exhibited a reduced transmigration response. Hence, when the ability of TNF-alpha to directly stimulate neutrophils is blocked, TNF-alpha-induced neutrophil transmigration is rendered dependent on ICAM-2, JAM-A, and PECAM-1, suggesting that the stimulus-dependent role of these molecules is governed by the target cell being activated. Furthermore, analysis of the site of arrest of neutrophils in inflamed tissues from ICAM-2(-/-), JAM-A(-/-), and PECAM-1(-/-) mice demonstrated that these molecules act sequentially to mediate transmigration. Collectively, the findings provide novel insights into the mechanisms of action of key molecules implicated in leukocyte transmigration.
Keywords AnimalsAntigens, CD/physiologyAntigens, CD31/physiologyCell AdhesionCell Adhesion Molecules/physiologyCell Movement/physiologyCells, CulturedEndothelium, Vascular/cytology/metabolismFluorescent Antibody TechniqueLeukocytes/cytology/metabolismMaleMiceMice, Inbred C57BLMice, KnockoutMuscles/cytology/metabolismNeutrophils/physiologyReceptors, Cell Surface/physiologyReceptors, Tumor Necrosis Factor, Type I/physiologyTumor Necrosis Factor-alpha/pharmacology
PMID: 19211506
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Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699241/?tool=pubmed
Research group Molécules d'adhésion et processus de migration cellulaire (167)
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WOODFIN, Abigail et al. Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1. In: Blood, 2009, vol. 113, n° 24, p. 6246-57. doi: 10.1182/blood-2008-11-188375 https://archive-ouverte.unige.ch/unige:5556

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Deposited on : 2010-03-24

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