Endotoxin Stimulates Synthesis of Platelet Activating Factor Via Production of Tumor Necrosis Factor by Human Mesangial Cells

Abstract

Gram negative sepsis commonly includes several manifestations such as fever, hypotension, intravascular coagulation, and acute oliguric renal failure (1). The sequence of events culminating in renal failure is only partially known. Release of endotoxin, composed of LPS from the outer membrane layer of gram-negative bacterial cell walls into the systemic circulation? leads to the enhanced production of biologically active substances such as angiotensin II, adenosine, interleukin-1, tumor necrosis factor (TNF), arachidonic acid metabolites and platelet- activating factor (PAF). Evidence has accumulated that endotoxin-induced hemodynamic dearrangements and inflammation is primarily mediated by IL-1 and TNF (2,3). We have recently shown that TNF stimulates rat peritoneal macrophages, human polymorphonuclear neutrophils and vascular endothelial cells to synthetize and release PAF ( ).