CD40-CD40L system as an example of platelet-endothelial interaction.
Shown are three endothelial cells and two platelets (not drawn to scale). Platelet activation results in increased expression of CD40 and CD40 ligand (CD40L). GPIIbIIIa-dependent adhesion of platelets to the endothelium results in CD40L-induced activation of endothelial cells with secondary induction of tissue factor, cytokines, adhesion molecules, metalloproteinases (MMP), urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), and urokinase receptor (u-PAR). Thus, the platelet indirectly orchestrates (via the endothelium) changes in coagulation, leukocyte trafficking, and extracellular matrix modeling/turnover. At the same time, the inter-action between platelet and endothelial cells results in GPIIbIIIa-mediated outside-in signaling with secondary induction of CD40L and CD62P (P-selectin) expression on the platelet surface. In addition, soluble trimeric CD40L (sCD40L), released from activated platelets, may engage platelet CD40 in an autocrine or paracrine manner (indicated by +), resulting in shape change and α-granule release.
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