Extracellular PAF exerts its actions by stimulating a specific GPCR that is expressed in numerous cell types. The PAF receptor's strict recognition requirements, including a specific head group and specific atypical sn-2 residue, also are met by oxPLs. The PAF receptor couples with Gg to activate the PLC-IP-Ca2+ pathway and phospholipases A2 and D such that AA is mobilized from diacylglycerol, resulting in the synthesis of PGs, TxA2, or LTs, which may function as extracellular mediators of the effects of PAF. PAF also may exert actions without leaving its cell of origin. For example, PAF is synthesized in a regulated fashion by endothelial cells stimulated by inflammatory mediators. This PAF is presented on the surface of the endothelium, where it activates the PAF receptor on juxtaposed cells, including platelets, polymorphonuclear leukocytes, and mono-cytes, and acts cooperatively with P-selectin to promote adhesion. Endothelial cells under oxidant stress release oxPLs, which activate leukocytes and platelets and can spread tissue damage.
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