Stimulation of peripheral blood leukocytes with lipopolysaccharide results in the synthesis of inflammatory cytokines including interleukin-1/3, interleukin-6, tumor necrosis factor-a and prostaglandin E, correlating with an increase in phospholipase A, activity. Mammalian cells contain several phospholipase A, isoforms including the 14-kDa secretory isoform and the more recently described high-molecular-mass cytosolic isoform. It is commonly believed that during inflammatory responses secretory phospholipase A, becomes activated. However, we could not detect secretory phospholipase A, nor its corresponding mRNA after lipopolysaccharide-induced activation. By contrast, we found increased mRNA levels for cytosolic phospholipase A, following activation of peripheral blood leukocytes when levels were compared to non-stimulated controls. Our results demonstrate that cytosolic phospholipase A,, rather than the secretory isoform may be the mediator of the lipopolysaccharide-induced inflammatory cascade in human peripheral blood leukocytes.Phospholipase A, is a lipolytic enzyme that hydrolyzes the fatty acyl ester at the sn-2 position of glycerophosphatides producing equimolar amounts of free fatty acids and lysophosphatides. The observation that arachidonic acid (A,Ach) is predominantly found esterified at the sn-2 position suggests that the action of this enzyme is the rate-limiting step in the synthesis of leukotrienes and prostaglandins. Furthermore, phospholipase A, is involved in the formation of platelet-activating factor [ 1, 21. These observations indicate that phospholipase A, plays a significant role in the synthesis of potent mediators of inflammation. Therefore, studies were initiated to correlate phospholipase A, levels in patients with different pathophysiological conditions. Evidence now indicates that elevated phospholipase A, levels are associated with diseases like acute pancreatitis, acute and chronic colitis, rheumatoid arthritis, allergic shock, septic shock, psoriasis and thrombotic cardiovascular diseases [3]. Experiments are therefore in progress to evaluate phospholipase A, activity and immunoreactivity as a diagnostic or prognostic marker for the above-mentioned diseases To date, the different phospholipase A, have been subdivided into two main classes, the secreted forms, including type I (pancreatic) and type I1 (secretory), and the nonsecreted forms, namely type IV (cytosolic) [7].Pharmacological research has focused primarily on secretory and cytosolic phospholipase A,, two isoforms which
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