Fadia R. Homaidan, Iman Chakroun, Hounaida Abi Haidar and Marwan E. El-Sabban Pages 467 - 484 ( 18 )
A variety of factors contribute to the complex course of inflammation. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of cytokines and inflammatory mediators are released. These factors activate, in addition to other signaling pathways, the lipid synthesis pathways, which play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the precursor of pro-inflammatory eicosanoids, is released from membrane phospholipids by the action of phospholipase A2 (PLA2), and is metabolized to prostaglandins (PGs) and leukotrienes (LTs) by the action of cyclooxygenase (COX) and lipoxygenase (LO) enzymes, respectively. Disordered activation of PLA2, LO and COX enzymes have been implicated in many inflammatory diseases. PLA2 is activated by phospholipase-A2-activating protein (PLAP) and LO by 5-lipoxygenase-activating protein (FLAP). The inducible form of COX-2 enzyme, which is usually not present under basal conditions, is induced in inflammation. In this article the function of these enzymes in eicosanoid synthesis, their regulation, and their implication in inflammatory disorders will be reviewed. The properties, function and regulation of the protein activators PLAP and FLAP will also be discussed.
Eicosanoid Synthesis, toxic agents, cyclooxygenase, 5-lipoxygenase-activating protein
Department of Physiology,American University of Beirut, 850 Third Ave, 18th Floor, New York, NY10022, USA