Fibrinogen deposition at the postischemic vessel wall promotes platelet adhesion during ischemia-reperfusion in vivo

Following ischemia-reperfusion (I/R), platelet adhesion is thought to repre sent the initial event leading to remodeling and reocclusion of the vascula ture. The mechanisms underlying platelet adhesion to the endothelium have n ot been completely established. Endothelial cells rendered ischemic acquire a procoagulant phenotype, characterized by fibrinogen accumulation. Theref ore, we evaluated whether fibrinogen deposition during I/R mediates platele t adhesion. Using fluorescence microscopy, fibrinogen deposition and the ac cumulation of platelets were assessed in vivo in a model of intestinal I/R (1.5 hours/60 minutes). Fibrinogen accumulated in arterioles and venules ea rly after the onset of reperfusion. The deposition of fibrinogen colocalize d with large numbers of adherent platelets (520 +/- 65 and 347 +/- 81 plate lets/mm(2) in arterioles and venules). Pretreatment with an antifibrinogen antibody attenuated platelet adhesion. Intracellular adhesion molecule (ICA M)-1 served as a major receptor for fibrinogen, since fibrinogen deposition and platelet adhesion to the endothelial cell surface were markedly decrea sed in ICAM-1-deficient mice. The platelet alpha(IIb)/beta(3) integrin play s a key role in fibrinogen-dependent platelet accumulation, because (1) pla telet adhesion involved RGD-recognition sequences, and (2) platelets isolat ed from a patient with Glanzmann's disease showed decreased interaction wit h the postischemic endothelium. Since platelets are demonstrated here to in duce tyrosine phosphorylation in endothelial cells, platelet recruitment mi ght contribute to the development of an inflammatory reaction during I/R. ( C) 1999 by The American Society of Hematology.