Characterization of luminal paneth cell <i>α</i>-defensins in mouse small intestine -: Attenuated antimicrobial activities of peptides with truncated amino termini

作     者：Ouellette, AJ Satchell, DP Hsieh, MM Hagen, SJ Selsted, ME 

作者机构：Univ Calif Irvine Coll Med Dept Pathol Irvine CA 92697 USA Univ Calif Irvine Coll Med Dept Microbiol & Mol Genet Irvine CA 92697 USA Beth Israel Deaconess Med Ctr Boston MA 02115 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2000年第275卷第43期

页      面：33969-33973页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NIDDK NIH HHS [DK 15681  DK44632  DK33506] Funding Source: Medline 

主　　题：抗菌药/分离和提纯 细菌/药物作用 免疫组织化学 小肠/化学 小鼠 近交ICR 蛋白质前体/化学 蛋白质前体/分离和提纯 蛋白质前体/药理学 构效关系 动物 小鼠 

摘      要：Paneth cells at the base of small intestinal crypts secrete apical granules that contain antimicrobial peptides including alpha -defensins, termed cryptdins, Using an antibody specific for mouse cryptdin-1, -2, -3, and -6, immunogold-localization studies demonstrated that cryptdins are constituents of mouse Paneth cell secretory granules. Several cryptdin peptides have been purified from rinses of adult mouse small. intestine by gel filtration and reverse-phase high performance liquid chromatography. Their primary structures were determined by peptide sequencing, and their antimicrobial activities were compared with those of the corresponding tissue forms. The isolated luminal cryptdins included peptides identical to the tissue forms of cryptdin-2, -4, and -6 as well as variants of cryptdin-1, -4, and -6 that have N termini truncated by one or two residues. In assays of antimicrobial activity against Staphylococcus aureus, Escherichia coli, and the defensin-sensitive Salmonella typhimurium phoP(-) mutant, full-length cryptdins had the same in vitro antibacterial activities whether isolated from tissue or from the lumen. In contrast, the N-terminal-truncated (des-Leu), (des-Leu-Arg)-cryptdin-6, and (des-Gly)-cryptdin-4 peptides mere markedly less active. The microbicidal activities of recombinant cryptdin-4 and (des-Gly)-cryptdin-4 peptides against E. coli, and S. typhimurium showed that the N-terminal Gly residue or the length of the cryptdin-4 N terminus are determinants of microbicidal activity. Innate immunity in the crypt lumen may be modulated by aminopeptidase modification of alpha -defensins after peptide secretion.