Cell adhesion mechanisms in platelets.
At sites of vascular injury, platelets come into contact with the subendothelial extracellular matrix which triggers their activation and the formation of a hemostatic plug. This process is crucial for normal hemostasis, but may also lead to pathological thrombus formation causing diseases such as myocardial infarction or stroke. The initial capture of flowing platelets is mediated by the interaction of the glycoprotein (GP) Ib-V-IX complex with von Willebrand factor (vWF) immobilized on exposed collagens. This interaction allows the binding of the collagen receptor GPVI to its ligand and to initiate cellular activation, a process that is reinforced by locally produced thrombin and soluble mediators released from platelets. These events lead to the shift of beta1 and beta3 integrins on the platelet surface from a low to a high affinity state, thereby enabling them to bind their ligands and to mediate firm adhesion, spreading, coagulant activity, and aggregation. This review summarizes the most important structural and functional properties of these adhesion receptors and briefly discusses their potential as targets for antithrombotic therapy.
Varga-Szabo
David
D
Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Zinklesweg 10, 97078 Würzburg, Germany.
Pleines
Irina
I
Nieswandt
Bernhard
B
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008967:Molecular Biology / Q000379:methods; D010973:Platelet Adhesiveness / Q000235:genetics / Q000502:physiology*; D010974:Platelet Aggregation / Q000235:genetics / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI