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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
| Content Provider | Scilit |
|---|---|
| Author | Woodfin, Abigail Voisin, Mathieu-Benoit Imhof, Beat A. Dejana, Elisabetta Engelhardt, Britta Nourshargh, Sussan |
| Copyright Year | 2009 |
| Description | 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699241/pdf |
| Ending Page | 6257 |
| Page Count | 12 |
| Starting Page | 6246 |
| DOI | 10.1182/blood-2008-11-188375 |
| Journal | Blood |
| Issue Number | 24 |
| Volume Number | 113 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2009-06-11 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Leukocytes Endothelial Cell Cell Adhesion Icam Jam Pecam Mice Neutrophil Transmigration Journal: Blood (Vol- 138, Issue- 24) |
| Content Type | Text |
| Resource Type | Article |
