Phospholipase A2 subclasses in acute respiratory distress syndrome.

Phospholipases A2 (PLA2) catalyse the cleavage of fatty acids esterified at the sn-2 position of glycerophospholipids. In acute lung injury-acute respiratory distress syndrome (ALI-ARDS) several distinct isoenzymes appear in lung cells and fluid. Some are capable to trigger molecular events leading to enhanced inflammation and lung damage and others have a role in lung surfactant recycling preserving lung function: Secreted forms (groups sPLA2-IIA, -V, -X) can directly hydrolyze surfactant phospholipids. Cytosolic PLA2 (cPLA2-IVA) requiring Ca2+ has a preference for arachidonate, the precursor of eicosanoids which participate in the inflammatory response in the lung. Ca(2+)-independent intracellular PLA2s (iPLA2) take part in surfactant phospholipids turnover within alveolar cells. Acidic Ca(2+)-independent PLA2 (aiPLA2), of lysosomal origin, has additionally antioxidant properties, (peroxiredoxin VI activity), and participates in the formation of dipalmitoyl-phosphatidylcholine in lung surfactant. PAF-AH degrades PAF, a potent mediator of inflammation, and oxidatively fragmented phospholipids but also leads to toxic metabolites. Therefore, the regulation of PLA2 isoforms could be a valuable approach for ARDS treatment.