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) involv ed nor the importance of blood components and/or different inflammator y cytokines has been clarified. In the present study, injection of end otoxin in rats caused increased lung levels of group II PLA(2), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta mRNA, while g roup I PLA(2) mRNA levels were unaffected. The augmented group II PLA( 2) mRNA levels corresponded to a rise in membrane-associated PLA(2) en zymatic 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 bet a mRNA levels and release of PLA(2) and TNF-alpha activity into the pe rfusate, and when instilled intratracheally, endotoxin caused increase d PLA(2) activity in the lung tissue. It is concluded that I) endotoxi n stimulates group II PLA(2), but not group I PLA(2), in rat lung cell s, 2) this stimulation is accompanied by increased expression of TNF-a lpha and IL-1 beta, and 3) endotoxin-induced PLA(2) activation and cyt okine production in the lung are not dependent on circulating blood co mponents.