| First Author | Wang HB | Year | 2007 |
| Journal | Nat Immunol | Volume | 8 |
| Issue | 8 | Pages | 882-92 |
| PubMed ID | 17632516 | Mgi Jnum | J:123408 |
| Mgi Id | MGI:3718272 | Doi | 10.1038/ni1491 |
| Citation | Wang HB, et al. (2007) P-selectin primes leukocyte integrin activation during inflammation. Nat Immunol 8(8):882-892 |
| abstractText | Selectins mediate leukocyte rolling and prime leukocytes for integrin-mediated leukocyte adhesion. However, neither the in vivo importance of nor the signaling pathway by which selectin-mediated integrin activation occurs has been determined. We report here that P-selectin-deficient mice manifested impaired leukocyte adhesion, which was 'rescued' by soluble P-selectin. Mechanistically, the cytoplasmic domain of P-selectin glycoprotein ligand 1 formed a constitutive complex with Nef-associated factor 1. After binding of P-selectin, Src kinases phosphorylated Nef-associated factor 1, which recruited the phosphoinositide-3-OH kinase p85-p110delta heterodimer and resulted in activation of leukocyte integrins. Inhibition of this signal-transduction pathway diminished the adhesion of leukocytes to capillary venules and suppressed peritoneal infiltration of leukocytes. Our data demonstrate the functional importance of this newly identified signaling pathway mediated by P-selectin glycoprotein ligand 1. |
