Study of Some Mechanisms that may Contribute to the Presence of High Levels of Phospholipase A2 Activity in Plasma of Patients with Septicemia

Abstract

Phospholipase A2 (EC 3.1.1.4) is a family of phosphatide 2-acylhydrolases that play an important role in the metabolism of phospholipids and membrane homeostasis [1–4]. These functions of phospholipase A2 seem relevant to the pathogenesis of various clinical conditions, since the presence of high concentrations of phospholipase A2 activity in plasma and inflammatory exudates of patients suffering from inflammatory arthritis, peritonitis and septic shock has been reported. Administration of exogenous extracellular phospholipase into experimental animals causes inflammatory hyperemia [5], and a correlation of serum levels of phospholipase A2 with the magnitude of hypotension has been shown in endotoxin shock [6,7]. The possible pathogenetic role of soluble phospholipase A2 in endotoxin shock in connection to the cytokine network has been emphasized by several reports showing the secretion of type II phospholipase A2 by rat mesangial cells [8,9], liver cells [1011] and human synovial cells [12,13] in response to tumor necrosis factor and interleukin ls. A recent report from this laboratory has shown the presence of high amounts of PAF associated with the platelets of patients with septicemia [14] and this raises the question as to whether this finding might be related to the secretion of phospholipase A2 activity and an ensuing formation of lipid mediators.