| First Author | Wu Y | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 6 | Pages | 3484-91 |
| PubMed ID | 16148090 | Mgi Jnum | J:116717 |
| Mgi Id | MGI:3694863 | Doi | 10.4049/jimmunol.175.6.3484 |
| Citation | Wu Y, et al. (2005) Neutrophils lacking platelet-endothelial cell adhesion molecule-1 exhibit loss of directionality and motility in CXCR2-mediated chemotaxis. J Immunol 175(6):3484-91 |
| abstractText | Time-lapsed videomicroscopy was used to study the migration of platelet-endothelial cell adhesion molecule-1-deficient (PECAM-1(-/-)) murine neutrophils undergoing chemotaxis in Zigmond chambers containing IL-8, KC, or fMLP gradients. PECAM-1(-/-) neutrophils failed to translocate up the IL-8, KC, and fMLP gradients. Significant reductions in cell motility and cell spreading were also observed in IL-8 or KC gradients. In wild-type neutrophils, PECAM-1 and F-actin were colocalized at the leading fronts of polarized cells toward the gradient. In contrast, in PECAM-1(-/-) neutrophils, although F-actin also localized to the leading front of migrating cells, F-actin polymerization was unstable, and cycling was remarkably increased compared with that of wild-type neutrophils. This may be due to the decreased cytokine-induced mobilization of the actin-binding protein, moesin, into the cytoskeleton of PECAM-1(-/-) neutrophils. PECAM-1(-/-) neutrophils also exhibited intracellularly dislocalized Src homology 2 domain containing phosphatase 1 (SHP-1) and had less IL-8-induced SHP-1 phosphatase activity. These results suggest that PECAM-1 regulates neutrophil chemotaxis by modulating cell motility and directionality, in part through its effects on SHP-1 localization and activation. |
