Activation Of Phospholipase A₂ in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA), a common and often disabling systemic disease with a predilection for joints, is characterized by an inflammatory and proliferative reaction of synovial cells associated with infiltration of immunocompetent cells and fluid into the synovial tissue, as well as the destruction of articular cartilage. Prostaglandins and related eicosanoids are thought to be important mediators and regulators of these immune and inflammatory responses (1, 2, 3). For example, prostaglandin E₂ induces bone resorption, and leukotriene B₄ stimulates vasodilitation and chemotaxis (1, 4). Increased quantities of eicosanoids are produced by rheumatoid synovium in both organ and cell culture (2, 5, 6) and by freshly isolated or cultured peripheral blood monocytes isolated from RA patients as compared to cells obtained from normal donors (7, 8, 9, 10). In addition, high concentrations of eicosanoids have been shown to be present in rheumatoid synovial fluid (2, 11, 12). Because eicosanoids are important mediators of this disease, numerous investigators have sought to understand the mechanisms of enhanced eicosanoid biosynthesis in this illness. The rate-limiting step in eicosanoid biosynthesis is the release of the precursor fatty acid from membrane phospholipids (4, 13, 14, 15, 16, 17). Once liberated, the unsaturated fatty acid, usually arachidonic acid, is then oxygenated to form prostaglandins, leukotrienes and related lipid metabolites.