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 represent the initial event leading to remodeling and reocclusion of the vasculature. The mechanisms underlying platelet adhesion to the endothelium have not been completely established. Endothelial cells rendered ischemic acquire a procoagulant phenotype, characterized by fibrinogen accumulation. Therefore, we evaluated whether fibrinogen deposition during I/R mediates platelet adhesion. Using fluorescence microscopy, fibrinogen deposition and the accumulation of platelets were assessed in vivo in a model of intestinal I/R (1.5 hours/60 minutes). Fibrinogen accumulated in arterioles and venules early after the onset of reperfusion. The deposition of fibrinogen colocalized with large numbers of adherent platelets (520 +/- 65 and 347 +/- 81 platelets/mm(2) in arterioles and venules). Pretreatment with an antifibrinogen antibody attenuated platelet adhesion. Intracellular adhesion molecule (ICAM)-1 served as a major receptor for fibrinogen, since fibrinogen deposition and platelet adhesion to the endothelial cell surface were markedly decreased in ICAM-1-deficient mice. The platelet alpha(IIb)/beta(3) integrin plays a key role in fibrinogen-dependent platelet accumulation, because (1) platelet adhesion involved RGD-recognition sequences, and (2) platelets isolated from a patient with Glanzmann's disease showed decreased interaction with the postischemic endothelium. Since platelets are demonstrated here to induce tyrosine phosphorylation in endothelial cells, platelet recruitment might contribute to the development of an inflammatory reaction during I/R.
Massberg
S
S
Ludwig-Maximilians-University, Institute for Surgical Research, Klinikum Grosshadern, Munich, Germany. massberg@icf.med.uni-muenchen.de
Enders
G
G
Matos
F C
FC
Tomic
L I
LI
Leiderer
R
R
Eisenmenger
S
S
Messmer
K
K
Krombach
F
F
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D010973:Platelet Adhesiveness; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen