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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
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) medi...
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| Main Authors: | , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
American Society of Hematology
2009
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| Assuntos: | |
| Acesso em linha: | https://ncbi.nlm.nih.gov/pmc/articles/PMC2699241/ https://ncbi.nlm.nih.gov/pubmed/19211506 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1182/blood-2008-11-188375 |
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| Resumo: | 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-1β [IL-1β] but not tumor necrosis factor-α [TNF-α]), and demonstrate their ability to act in sequence. Using a cell-transfer technique, transmigration responses of wild-type and TNF-α 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-α in ICAM-2(−/−), JAM-A(−/−), and PECAM-1(−/−) recipient mice, TNFR(−/−) leukocytes exhibited a reduced transmigration response. Hence, when the ability of TNF-α to directly stimulate neutrophils is blocked, TNF-α–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. |
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