Endotoxin stimulates the expression of group II PLA(2) in rat lung in vivo and in isolated perfused lungs

Injection of endotoxin in vivo leads to increased phospholipase A(2) (PLA(2)) activity in the lung, but neither the type(s) of PLA(2) involved nor the importance of blood components and/or different inflammatory cytokines has been clarified. In the present study, injection of endotoxin in rats caused increased lung levels of group II PLA(2), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta mRNA, while group I PLA(2) mRNA levels were unaffected. The augmented group II PLA(2) mRNA levels corresponded to a rise in membrane-associated PLA(2) enzymatic activity that was inhibited by rutin, an inhibitor of group II PLA(2). In blood-free, salt-perfused lungs, addition of endotoxin to the perfusate caused elevated group II PLA(2), TNF-alpha, and IL-1 beta mRNA levels and release of PLA(2) and TNF-alpha activity into the perfusate, and when instilled intratracheally, endotoxin caused increased PLA(2) activity in the lung tissue. It is concluded that I) endotoxin stimulates group II PLA(2), but not group I PLA(2), in rat lung cells, 2) this stimulation is accompanied by increased expression of TNF-alpha and IL-1 beta, and 3) endotoxin-induced PLA(2) activation and cytokine production in the lung are not dependent on circulating blood components.