New mechanisms by which secretory phospholipase A2 stimulates neutrophils to provoke the release of cytotoxic agents.

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Abstract
CIRCULATING LEVELS of secretory phospholipase A2 (sPLA2) have recently been identified as a sensitive marker of injured and septic patients at risk for multiple organ failure (MOF).1-5 The magnitude of sPLA2 elevation correlates with the development of the adult respiratory distress syndrome and with MOF.6-10 Our animal models of gut ischemia and reperfusion have demonstrated the importance of the enzymatic function of PLA2 in producing lung and liver injury.11 Other animal models of sepsis have shown that enzymatic inhibitors of sPLA2 improve survival.12-14 However, results of trials using enzymatic inhibitors of sPLA2 in the clinical setting have been disappointing.15 The link between sPLA2 and inflammation has been attributed to its calcium-dependent enzymatic function. Secretory PLA2 catalyzes the hydrolysis of the 2-ester bond of 3-sn-phosphoglycerides.16 This produces reactive lipid mediators such as platelet-activating factor and arachidonic acid. Previous work has focused on sPLA2 cleavage of plasma lipids to activate inflammatory cells.17,18 However, the exact mechanism of cellular activation remains unclear.