P-selectin primes leukocyte integrin activation during inflammation

Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Nature Immunology (Impact Factor: 24.97). 09/2007; 8(8):882-92. DOI: 10.1038/ni1491
Source: PubMed

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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Available from: Tao Xu, Mar 18, 2014
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    • "j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / t h ro m re s L-selectin in leukocytes (as it was believed earlier) as well as in trophoblasts (as found out later) [5]. The pathophysiologic factors can activate endothelial cells, blood platelets and leukocytes, which results in selectin expression on the cell membrane, followed by intracellular interaction (in the case of complications a cascade of cellular events can be observed, including tethering and rolling of leukocytes on the vascular wall, their subsequent firm adhesion or transmigration [6] ). As for the lack of E-selectin in the amniotic fluid, we may assume, based on the data concerning the selectin sources, (a) that the amnion cells, lining the interior of the amnion sac and having a direct contact with the amniotic fluid, do not synthesize E-selectin (as it would be released to the fluid), and (b) that this substance is also missing in the nasopharyngeal/bronchial secretions and urine excretion of the fetus that pass to the amniotic fluid [7]. "
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