SECRETION OF TYPE-II PHOSPHOLIPASE A(2) AND CRYPTDIN BY RAT SMALL-INTESTINAL PANETH CELLS

We examined the secretion of antimicrobial proteins and peptides into surgically isolated and continuously perfused segments of rat smell in testine, Up to nine discrete antimicrobial molecules appeared in the i ntestinal perfusates following intravenous administration of bethanech ol, a cholinergic agonist, or intralumenal instillation of lipopolysac charide (LPS), Among them were three markers of Paneth cell secretion: lysozyme; type II (secretory) phospholipase A,; and at least one inte stinal defensin, RIP-3, that appeared to be an alternatively processed variant of the rat neutrophil defensin RatNP-3, Both bethanechol- and UPS-stimulated intestinal lumenal perfusates (washings) contained mol ecules that killed Escherichia coli, Salmonella typhimurium, and Liste ria monocytogenes in vitro, These molecules were more active against t he avirulent S, typhimurium strain 7953S (phoP) than against its virul ent parent, S, typhimurium 14028S, These data demonstrate that small i ntestinal Paneth cells secrete antimicrobial peptides in vivo, that th is secretion is regulated by the autonomic (parasympathetic) cholinerg ic nervous system, and that the release of antimicrobial molecules can be triggered by the presence of bacterial LPS in the intestinal lumen .