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 lß. 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.