P-selectin primes leukocyte integrin activation during inflammation

Hai Bo Wang, 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

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122 Scopus citations

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-p110δ 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.

Original languageEnglish (US)
Pages (from-to)882-892
Number of pages11
JournalNature Immunology
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 1 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Wang, H. B., Wang, J. T., Zhang, L., Geng, Z. H., Xu, W. L., Xu, T., ... Geng, J. G. (2007). P-selectin primes leukocyte integrin activation during inflammation. Nature Immunology, 8(8), 882-892. https://doi.org/10.1038/ni1491