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P-selectin primes leukocyte integrin activation during inflammation.

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.

Pubmed ID: 17632516


  • Wang HB
  • Wang JT
  • Zhang L
  • Geng ZH
  • Xu WL
  • Xu T
  • Huo Y
  • Zhu X
  • Plow EF
  • Chen M
  • Geng JG


Nature immunology

Publication Data

August 20, 2007

Associated Grants

  • Agency: NHLBI NIH HHS, Id: P50HL081011
  • Agency: NIAID NIH HHS, Id: R01AI064743

Mesh Terms

  • Animals
  • Cell Adhesion
  • Chemotaxis, Leukocyte
  • DNA-Binding Proteins
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Inflammation
  • Integrins
  • Leukocytes
  • Membrane Glycoproteins
  • Mice
  • P-Selectin
  • Phosphatidylinositol 3-Kinases
  • Signal Transduction
  • Transfection