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. 2007 Aug;8(8):882-92.
doi: 10.1038/ni1491. Epub 2007 Jul 15.

P-selectin primes leukocyte integrin activation during inflammation

Hai-Bo Wang  1 , Jin-Tao Wang, Lei Zhang, Zhen H Geng, Wei-Li Xu, Tao Xu, Yuqing Huo, Xueliang Zhu, Edward F Plow, Ming Chen, Jian-Guo Geng
Affiliations

P-selectin primes leukocyte integrin activation during inflammation

Hai-Bo Wang et al. Nat Immunol. 2007 Aug.

Erratum in

  • Nat Immunol. 2014 Mar;15(3):305

Abstract

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.

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