Receptor cleavage and P-selectin-dependent reduction of leukocyte adhesion in the spontaneously hypertensive rat.

Journal of Leukocyte Biology
Angela Y ChenGeert W Schmid-Schönbein

Abstract

The SHR, a genetic model for hypertension and the metabolic syndrome, has attenuated leukocyte adhesion to the postcapillary endothelium by an unknown mechanism. Based on recent evidence of elevated levels of MMPs in plasma and on microvascular endothelium of the SHR with cleavage of several receptor types, we hypothesize that the reduced leukocyte-endothelial interaction is a result of enhanced proteolytic cleavage of P-selectin on the postcapillary endothelium and PSGL-1 on leukocytes. The attenuated rolling interactions of SHR leukocytes with the endothelium were restored by chronic treatment with a broad-spectrum MMP inhibitor (CGS) for 24 weeks. The SHR MMP levels, in plasma and mesentery, as well as the systolic blood pressure, decreased significantly with treatment. In the SHR mesentery, labeling of P-selectin in the postcapillary venules by immunohistochemistry demonstrated, on average, a 31% lower extracellular P-selectin density compared with the normotensive WKY. A significantly lower extracellular PSGL-1 density on the membranes of SHR neutrophils compared with the WKY also supported our hypothesis. In vivo stimulation of the mesenteric postcapillary venules with histamine demonstrated that the SHR had an attenuated...Continue Reading

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Citations

Aug 31, 2013·Annals of Biomedical Engineering·Geert W Schmid-Schönbein, Marisol Chang
Mar 8, 2014·Critical Care : the Official Journal of the Critical Care Forum·Rens ZonneveldChristopher V Carman
Dec 8, 2015·Frontiers in Cellular Neuroscience·Karoline MöllerDaniel-Christoph Wagner
Aug 31, 2014·Microvascular Research·Marco H SantamariaGeert W Schmid-Schönbein
Mar 21, 2018·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Selma Cirrik, Geert W Schmid-Schönbein
Apr 5, 2019·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Amy Hsueh Wen Chan, Geert W Schmid-Schönbein
Mar 17, 2017·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hidenori TakahashiMakoto Araie

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