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Rosenkranz, AR; Mendrick, DL; Cotran, RS; Mayadas, TN.
P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation.
J Clin Invest. 1999; 103(5):649-659 Doi: 10.1172/JCI5183 [OPEN ACCESS]
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Leading authors Med Uni Graz: Rosenkranz Alexander
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Abstract:: P-selectin is a leukocyte adhesion receptor present in endothelial cells and platelets. We examined the role of P-selectin in the autologous phase of an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis using P-selectin-deficient mice and chimeric mice expressing P-selectin only in platelets or endothelial cells. P-selectin-deficient mice exhibited more severe glomerular damage with increased interstitial mononuclear leukocytic infiltrates, and had significantly increased proteinuria and mortality when compared to wild-type mice. P-selectin on the endothelium was predominantly responsible for protection from the exacerbated disease, because chimeric mice with endothelial P-selectin, and not mice with platelet P-selectin, showed glomerular injury similar to that in wild-type animals. Levels of soluble circulating P-selectin were increased in nephritic wild-type mice and in chimeric mice with endothelial P-selectin, but not platelet P-selectin. Levels of soluble P-selectin, which has been shown to be anti-inflammatory in vitro, were inversely associated with the severity of disease. P-selectin was not expressed in the endothelium of the glomerulus or interstitium. Thus, the protective effect in wild-type mice may be accounted for, in part by soluble P-selectin shed by non-renal endothelial cells, although other endothelial P-selectin-dependent mechanisms cannot be ruled out.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Anti-Glomerular Basement Membrane Disease - genetics Anti-Glomerular Basement Membrane Disease - immunology Anti-Glomerular Basement Membrane Disease - pathology; Endothelium, Vascular - immunology Endothelium, Vascular - pathology; Immunohistochemistry -; Inflammation - genetics Inflammation - immunology Inflammation - pathology; Mice -; Mice, Inbred C57BL -; Mice, Knockout -; P-Selectin - genetics P-Selectin - immunology