NOVEL DEFENSINS IN HUMAN EPITHELIAL TISSUE

描述(从申请人的摘要改编和修改)：出现 对抗生素耐药微生物的研究引起了极大的兴趣 内源性抗菌物质及其调控机制 在人类身上的表达。防御素是富含半胱氨酸的阳离子多肽 从包括人类在内的几种哺乳动物中分离出来，具有广谱 抗菌活性。肠上皮是一种连续的表面 接触管腔内容物不同程度地携带微生物，但感染 不同寻常。研究人员提出，上皮防御素可以是 分成两个不同的结构子家族，分别命名为α-和 β-，有助于肠道粘膜的抗菌防御。 此外，他提出，有不同的战略用途 这两个亚家族的防御素在小肠和结肠，在 结构/功能术语，表达的解剖模式和类型 监管。研究人员认为，这些差异已经演变成 在这两个截然不同的环境中完成主机防御。至 为了解决这些假设，研究人员建议将 人类小分子主要防御素的结构特征 肠道和结肠组织，测定其体外抗菌活性 活动，以便将结构和功能联系起来，并使用 肠源性防御素表达作为检测其反应表达的工具 对炎性刺激。上皮防御素多肽可能会装备 具有以前未知的防御能力的粘膜表面 补充了其他定义明确的抗菌防御措施。确定 利用这些抗菌剂进化出的防御策略 多肽将增强我们对基本寄主防御机制的理解 可能会导致有用的疗法的发展。

DESCRIPTION (Adapted and modified from applicant's abstract): The emergence of antibiotic-resistant microorganisms has heightened interest in the study of endogenous antimicrobial substances and the mechanisms regulating their expression in humans. Defensins are cysteine-rich cationic peptides isolated from several mammals, including humans, with broad-spectrum antimicrobial activity. The intestinal epithelium is a surface in continual contact with luminal contents variably laden with microbes, yet infection is uncommon. The investigator proposes that epithelial defensins, which can be grouped into two distinct structural subfamilies, designated alpha- and beta-, contribute to antimicrobial defense of the enteric mucosa. Furthermore, he proposes that there is a different strategic utilization of these two subfamilies of defensins in the small intestine and colon, in terms of structure/function, anatomical patterns of expression and types of regulation. The investigator suggests that these differences have evolved to accomplish host defense in these two very different environments. To address these hypotheses, the investigator proposes to isolate and structurally characterize the predominant defensins from human small intestinal and colonic tissues, determine their in vitro antimicrobial activity in order to relate structure and function, and use model systems of enteric defensin expression as tools to examine their expression in response to inflammatory stimuli. Epithelial defensin peptides are likely to equip mucosal surfaces with a previously unrecognized defensive capability that complements other well-defined antimicrobial defenses. Determining the strategies of defense that have evolved utilizing these antimicrobial peptides will enhance our understanding of basic host defense mechanisms and may lead to the development of useful therapeutics.