Erratum: 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: 20). 09/2007; 8(8):882-92. DOI: 10.1038/ni1491
Source: PubMed


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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    • "We have previously demonstrated that the elevated levels of sP-selectin present in patients with peripheral vascular disease is not only a biomarker of disease but has functional effects by activating leukocytes and promoting their adhesion to platelet monolayers [14]. We have also shown that sP-selectin promotes leukocyte adhesion through PSGL-1 outside-in signalling through Src and PI3K, leading to Mac-1 integrin activation and subsequent recruitment to arterial and venule micro- and macro-circulation [15], a finding described by others [16]. "
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    ABSTRACT: Soluble P-selectin (sP-selectin), a biomarker of inflammatory related pathologies including cardiovascular and peripheral vascular diseases, also has pro-atherosclerotic effects including the ability to increase leukocyte recruitment and modulate thrombotic responses in vivo. The current study explores its role in progressing atherosclerotic plaque disease. Apoe-/- mice placed on a high fat diet (HFD) were given daily injections of recombinant dimeric murine P-selectin (22.5 µg/kg/day) for 8 or 16 weeks. Saline or sE-selectin injections were used as negative controls. In order to assess the role of sP-selectin on atherothrombosis an experimental plaque remodelling murine model, with sm22α-hDTR Apoe-/- mice on a HFD in conjunction with delivery of diphtheria toxin to induce targeted vascular smooth muscle apoptosis, was used. These mice were similarly given daily injections of sP-selectin for 8 or 16 weeks. While plaque mass and aortic lipid content did not change with sP-selectin treatment in Apoe-/- or SM22α-hDTR Apoe-/- mice on HFD, increased plasma MCP-1 and a higher plaque CD45 content in Apoe-/- HFD mice was observed. As well, a significant shift towards a more unstable plaque phenotype in the SM22α-hDTR Apoe-/- HFD mice, with increased macrophage accumulation and lower collagen content, leading to a lower plaque stability index, was observed. These results demonstrate that chronically raised sP-selectin favours progression of an unstable atherosclerotic plaque phenotype.
    Full-text · Article · May 2014 · PLoS ONE
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    • "Thus, activated platelet interaction with PSGL-1 on monocytes promotes an inflammatory reaction by COX-2/mPGES-1 expression and this effect may contribute to plaque destabilization [122]. In addition to P-selectin- PSGL1 (platelet-leukocyte) interaction [123], RAGE-Mac-1 interaction defines a novel pathway of leukocyte recruitment relevant in inflammatory disorders associated with increased RAGE expression [33] [124]. Strikingly, leukocyte adhesion in acutely inflamed venules almost completely disappears in the absence of RAGE [125]. "
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    ABSTRACT: In the context of plaque progression, platelet hyperactivity associated with hyperlipidemia contributes to the development of a pro-thrombotic state. In this context, it has been demonstrated that advanced glycation end products (AGEs) significantly increases platelet activation and receptor for AGEs (RAGE) expression at the platelet surface membrane. In addition to AGEs, other ligands (S100, HMGB1 and amyloid β, among others) of RAGE have raised particular attention in platelet activation. Therefore, in this article we describe platelet hyperactivity by AGEs via RAGE-independent and RAGE-dependent pathways.
    Full-text · Article · Nov 2013 · Thrombosis Research
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    • "When P-selectin combines with corresponding ligands on the surface of leukocytes, it causes the slow rolling of leukocytes, which ultimately causes an increased concentration of white blood cells in inflamed areas (9). Studies using P-selectin-deficient rats revealed a serious disorder of leukocyte adhesion function in these rats, suggesting that CD62p has a role in white blood cells to mediate leukocyte activation and adhesion and to release inflammatory substances (10). P-selectin aids the reperfusion of injuries following ischemia and promotes the formation of atherosclerosis. "
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    ABSTRACT: The aim of this study was to analyze the association between plasma-soluble P-selectin (sP-selectin) elements and progressive ischemic stroke (PIS) and to explore the pathogenesis of PIS. Patients with acute ischemic stroke who were admitted and hospitalized in the Department of Neurology between August 2010 and August 2011 were used as subjects in this study. The enrolled patients were divided into progressive (58 cases) and non-progressive groups (143 cases), based on changes in disease conditions. The normal control group included 40 cases. The sP-selectin levels and related risk factors of the three groups of patients were compared. sP-selectin levels in the progressive group showed the highest values on day 1 after progression and gradually decreased on days 3, 7 and 14. sP-selectin levels in the progressive and non-progressive groups on day 1 were higher compared with those in the control group (P<0.05) and the levels in the progressive group were higher compared with those in the non-progressive group (P<0.05). On days 3 and 7, levels in the progressive group were higher compared with those in the non-progressive group (P<0.05) and on day 14, levels in the progressive group remained higher compared with those in the non-progressive group (P>0.05). On days 1, 3 and 7, sP-selectin levels in the aortic atherosclerosis progressive group were higher compared with those in the aortic atherosclerosis non-progressive group (P<0.05), however on day 14, the difference between the two groups was not statistically significant (P>0.05). P-selectin levels had the most significant impact on the progressive group and the aortic atherosclerosis progressive group. P-selectin levels were high in patients with PIS and even higher in the aortic atherosclerosis progressive group and were closely correlated with the onset time of PIS.
    Full-text · Article · May 2013 · Experimental and therapeutic medicine
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