Bactericidal properties of murine intestinal phospholipase A2.
We purified a molecule from the murine small intestine that killed both Escherichia coli and Listeria monocytogenes, and identified it as intestinal phospholipase A2 (iPLA2) by NH2-terminal sequencing and enzymatic measurements. The ability of iPLA2 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 iPLA2-mediated bactericidal activity. A mouse-avirulent phoP mutant, S. typhimurium 7953S, was 3.5-fold more susceptible to iPLA2 than its isogenic virulent parent, S. typhimurium 14028S (estimated minimal bactericidal concentrations 12.7 +/- 0.5 micrograms/ml vs. 43.9 +/- 4.5 micrograms/ml P < 0.001). Overall, these findings identify iPLA2 as part of the antimicrobial arsenal that equips Paneth cells to protect the small intestinal crypts from microbial invasion. Because iPLA2 is identical to Type 2 phospholipase A2 molecules found in other sites, including spleen, platelets and inflammatory exudate cells, this enzyme may also contribute to antibacterial defenses elsewhere in the body.
Harwig
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SS
Department of Medicine, UCLA School of Medicine 90024.
Tan
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L
Qu
X D
XD
Cho
Y
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Eisenhauer
P B
PB
Lehrer
R I
RI
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004530:Egg Yolk; D004533:Egtazic Acid / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects*; D005260:Female; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology*; D007421:Intestine, Small / Q000166:cytology / Q000201:enzymology*; D008089:Listeria monocytogenes / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology; D010741:Phospholipases A / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054467:Phospholipases A2
D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D004533:Egtazic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium