Role of gut flora on intestinal group II phospholipase A(2) activity and intestinal injury in shock

We previously showed that group II phospholipase A(2) (PLA(2)-II), a secret ory, bactericidal, and proinflammatory protein in intestinal crypts, is upr egulated after lipopolysaccharide (LPS) and platelet-activating factor (PAF ) challenge. Here we examined whether germ-free environment (GF) or antibio tic treatment (ABX) affects the pathophysiological responses and intestinal PLA(2)-II activity after PAF (1.5 mug/kg) or LPS (8 mg/kg) injection. We f ound that LPS and PAF induced hypotension and mild intestinal injury in con ventionally fed (CN) rats; these changes were milder in ABX rats, whereas G F rats showed no intestinal injury. PLA(2)-II enzyme activity was detected in normal rat small intestine; the basal level was not diminished in ABX or GF rats. PAF and LPS caused an increase in PLA(2)-II activity, which was a brogated in GF and ABX rats. Recolonization of GF rats by enteral contamina tion restituted their PLA(2)-II response to PAF and LPS and susceptibility to bowel injury. We conclude that PAF- and LPS-induced increases in PLA(2)- II activity are dependent on gut bacteria, and ABX and GF rats are less sus ceptible to LPS-induced injury than CN rats.