Platelets modulate ischemia/reperfusion-induced leukocyte recruitment in the mesenteric circulation
Autor: | D. Neil Granger, Andrew C. Issekutz, James W. Salter, Christian F. Krieglstein |
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Rok vydání: | 2001 |
Předmět: |
Blood Platelets
Male medicine.medical_specialty Pathology P-selectin Physiology Platelet Glycoprotein GPIIb-IIIa Complex Fibrinogen Antibodies Microcirculation Rats Sprague-Dawley Immunoglobulin Fab Fragments Mesenteric Veins Physiology (medical) Internal medicine Mesenteric Vascular Occlusion medicine Cell Adhesion Leukocytes Animals Platelet Splanchnic Circulation Cell adhesion Peroxidase Venule Hepatology biology Gastroenterology Antibodies Monoclonal Mesenteric Arteries Rats Chemotaxis Leukocyte P-Selectin Endocrinology Myeloperoxidase Reperfusion Injury biology.protein Oligopeptides Intravital microscopy medicine.drug |
Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 281(6) |
ISSN: | 0193-1857 |
Popis: | P-selectin-dependent leukocyte-endothelial cell adhesion has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds, including the gut. Because platelet-endothelial (P/E) cell adhesion also occurs in postischemic venules, the possibility exists that the expression of P-selectin on the surface of platelets that are adherent to venular endothelial cells may mediate the leukocyte recruitment elicited by I/R. P-selectin expression [dual radiolabeled monoclonal antibody (MAb) technique] and neutrophil accumulation [myeloperoxidase (MPO) activity] were measured in the postischemic small intestine of untreated rats and rats treated with either antiplatelet serum (APS) or MAbs directed against either P-selectin, GPIIb/IIIa, or fibrinogen. The increases in P-selectin expression and tissue MPO normally elicited by I/R were significantly attenuated in the different treatment groups, suggesting that I/R-induced neutrophil recruitment is a platelet-dependent, P-selectin-mediated process. Intravital microscopy was then employed to examine this process relative to leukocyte-endothelial cell adhesion in postischemic rat mesenteric venules. The recruitment of adherent and emigrated leukocytes after I/R was attenuated by pretreatment with a MAb against, either P-selectin, GPIIb/IIIa, or fibrinogen, as well as an Arg-Gly-Asp peptide. Whereas thrombocytopenia greatly blunted leukocyte emigration, it did not alter the leukocyte adherence response to I/R. These findings suggest that platelet-associated P-selectin contributes to the accumulation of leukocytes in postischemic tissue via a mechanism that alters transendothelial leukocyte migration. |
Databáze: | OpenAIRE |
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