Phospholipase A2 isoforms, substrate specificity, and their role in inflammatory lipid mediator production in various disease states

Abstract

Phospholipase A2 enzymes catalyze the hydrolysis of membrane phospholipids at the sn-2 position, releasing arachidonic acid and lysophospholipids that serve as precursors for potent inflammatory mediators. This research investigated the substrate specificity and expression patterns of major phospholipase A2 isoforms in various inflammatory disease states. Serum samples and tissue biopsies were obtained from patients with rheumatoid arthritis, asthma, and inflammatory bowel disease attending clinics at Kuala Lumpur General Hospital between June 2022 and March 2023. Secretory, cytosolic, and calcium-independent phospholipase A2 activities were quantified using radiolabeled phospholipid substrates. Secretory PLA2 showed highest activity toward phosphatidylcholine, while cytosolic PLA2 preferentially hydrolyzed phosphatidylethanolamine. Patients with active rheumatoid arthritis demonstrated 3.4-fold elevated secretory PLA2 activity compared to healthy controls. Synovial fluid from arthritic joints showed marked enrichment of prostaglandin E2 and leukotriene B4 correlating with PLA2 activity levels. These findings confirm the central role of phospholipase A2 isoforms in inflammatory lipid mediator production and support their potential as therapeutic targets for anti-inflammatory intervention.