Interactions of platelets with subendothelium and endothelium.
In this review, the authors summarize how platelets interact with subendothelium when the vessel wall is damaged or with intact endothelium in the inflammatory state. When subendothelium is exposed to rapidly flowing blood upon vessel damage, platelets adhere rapidly to the exposed surface, decelerate, and aggregate to arrest bleeding. Under high shear stress, such as is found in the microcirculation, the interaction between subendothelial von Willebrand factor (VWF) and its platelet receptor, glycoprotein (GP) Ib-IX-V, is required to slow down platelets and allow the platelet collagen receptors aloha2beta1 and GP VI to bind to collagen. GP VI and alpha2beta1 play important roles to activate platelets in the early stage and work with GP Ib-IX-V to fully activate platelets to form thrombi. GP Ib-IX-V and GP VI employ similar signaling pathways for platelet activation and the signals from both receptors are down-modulated by PECAM-1 (platelet-endothelial-cell adhesion molecule 1) to prevent unnecessary platelet activation under high shear. During inflammatory states, intact endothelial cells release VWF and P-selectin from their Weibel-Palade bodies. Both molecules are ligands for GP Ib-IX-V. The newly released VWF is larger and stickier than the form normally found in plasma and binds platelets spontaneously. Normally, VWF is processed by proteolysis by the plasma metalloprotease ADAMTS-13. Failure of this processing results in the microvascular thrombotic disorder thrombotic thrombocytopenic purpura. In this review, the authors also use available crystal structures of platelet receptors and ligands to explain the details of their interactions.
Chen
Junmei
J
Department of Medicine Thrombosis Research Section, Baylor College of Medicine, Houston, Texas 77030, USA.
López
José A
JA
D001792:Blood Platelets / Q000166:cytology* / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D038981:Receptors, Collagen / Q000737:chemistry / Q000502:physiology; D014841:von Willebrand Factor / Q000737:chemistry / Q000502:physiology
D019038:Platelet Glycoprotein GPIb-IX Complex; D038981:Receptors, Collagen; D014841:von Willebrand Factor