BACTERICIDAL PROPERTIES OF MURINE INTESTINAL PHOSPHOLIPASE A(2)

We purified a molecule from the murine small intestine that killed both Escherichia coli and Listeria monocytogenes, and identified it as intestinal phospholipase A(2) (iPLA(2)) by NH2-terminal sequencing and enzymatic measurements. The ability of iPLA(2) to kill. L. monocytogenes was greatly enhanced by 5 mM calcium, inhibited by EGTA and abolished after reduction and alkylation, suggesting that enzymatic activity was required for iPLA(2)-mediated bactericidal activity. A mouse-avirulent phoP mutant, S. typhimurium 7953S, was 3.5-fold more susceptible to iPLA, than its isogenic virulent parent, S. typhimurium 14028S (estimated minimal bactericidal concentrations 12.7+/-0.5 mu g/ml vs. 43.9+/-4.5 mu g/ml, P < 0.001). Overall, these findings identify iPLA(2) as part of the antimicrobial arsenal that equips Paneth cells to protect the small intestinal crypts from microbial invasion. Because iPLA(2) is identical to Type 2 phospholipase A(2) molecules found in other sites, including spleen, platelets and inflammatory exudate cells, this enzyme may also contribute to antibacterial defenses elsewhere in the body.