Qu X D, Lloyd K C, Walsh J H, Lehrer R I
Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095-1690, USA.
Infect Immun. 1996 Dec;64(12):5161-5. doi: 10.1128/iai.64.12.5161-5165.1996.
We examined the secretion of antimicrobial proteins and peptides into surgically isolated and continuously perfused segments of rat small intestine. Up to nine discrete antimicrobial molecules appeared in the intestinal perfusates following intravenous administration of bethanechol, a cholinergic agonist, or intralumenal instillation of lipopolysaccharide (LPS). Among them were three markers of Paneth cell secretion: lysozyme; type II (secretory) phospholipase A2; and at least one intestinal defensin, RIP-3, that appeared to be an alternatively processed variant of the rat neutrophil defensin RatNP-3. Both bethanechol- and LPS-stimulated intestinal lumenal perfusates (washings) contained molecules that killed Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes in vitro. These molecules were more active against the avirulent S. typhimurium strain 7953S (phoP) than against its virulent parent, S. typhimurium 14028S. These data demonstrate that small intestinal Paneth cells secrete antimicrobial peptides in vivo, that this secretion is regulated by the autonomic (parasympathetic) cholinergic nervous system, and that the release of antimicrobial molecules can be triggered by the presence of bacterial LPS in the intestinal lumen.
我们研究了抗菌蛋白和肽在手术分离并持续灌注的大鼠小肠段中的分泌情况。静脉注射胆碱能激动剂氨甲酰甲胆碱或肠腔内滴注脂多糖（LPS）后，肠灌流液中出现了多达九种不同的抗菌分子。其中包括潘氏细胞分泌的三种标志物：溶菌酶；II型（分泌型）磷脂酶A2；以及至少一种肠道防御素RIP-3，它似乎是大鼠中性粒细胞防御素RatNP-3的一种可变加工变体。氨甲酰甲胆碱和LPS刺激后的肠腔灌流液（冲洗液）中所含的分子在体外能够杀死大肠杆菌、鼠伤寒沙门氏菌和单核细胞增生李斯特菌。这些分子对无毒力的鼠伤寒沙门氏菌菌株7953S（phoP）的活性比对其有毒力的亲本菌株鼠伤寒沙门氏菌14028S更强。这些数据表明，小肠潘氏细胞在体内分泌抗菌肽，这种分泌受自主（副交感）胆碱能神经系统调节，并且肠腔内细菌LPS的存在可触发抗菌分子的释放。
