Interactions of Platelet Activating Factor and Prostaglandins in the Glomerulus and in Mesangial Cells

Platelet activating factor (PAF) has been recognized as a potent mediator of inflammation and identified as l-alkyl-2-acetyl-sn-glycero-3-phospho-choline (Fig. 1). For biological activity, PAF requires an alkyl chain linked by an ether bond at the sn-1 position (most commonly a C16 length saturated chain) and an acetyl group at the sn-2 position. Loss of the acetyl group yielding lyso-PAF is associated with loss of biological activity (1–3). Many inflammatory cells have the capability to produce PAF upon stimulation, including peripheral leucocytes, with the exception of lymphocytes (1). Furthermore, cultured endothelial cells and renal cells (see below) can generate PAF. Stimuli that result in PAF formation cause an increase in intracellular calcium and include calcium ionophore, receptor-mediated phagocytosis or endocytosis, complement component C5a , formyl — methionyl — leucyl — phenyl — alanine and endotoxin (1–3). In general, resting cells do not produce PAF but require prior stimulation. Upon stimulation, PAF formation occurs via deacylation by phospholipase A2 of the precursor molecule l-alkyl-2-acyl-sn-glycero-3-phosphocholine to yield lyso PAF (Fig. 2). Lyso PAF is subsequently acetylated in position 2 by a specific acetyl-coenzyme A transferase to yield the active PAF molecule (1).