MICROBICIDAL ACTIVITY OF LEUKOCYTES--ACTIVE FACTORS

白细胞的杀菌活性--活性因子

• 批准号: 2713324
• 负责人: JERROLD P WEISS
• 金额: $ 41.25万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-06-23 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2713324
• 关键词: bactericidal immunity; binding proteins; disease /disorder model; exudate /transudate; genetic library; gram negative bacteria; human tissue; inflammation; laboratory rabbit; leukocytes; lipopolysaccharides; neutrophil; peritonitis; protein biosynthesis; protein isoforms; protein purification; protein structure function; protein transport; proteins; recombinant proteins; site directed mutagenesis; tissue /cell culture

DESCRIPTION (Adapted from applicant's abstract): This proposal concerns the further structural and functional characterization of two lipopolysaccharide (LPS)-binding antimicrobial protein from PMNs, the bactericidal/permeability increasing protein (BPI) and the 15 kDa protein isoforms (p15s), and the study of the role and regulation of BPI and p15 function in inflammatory exudates. These proteins have been isolated and cloned in this laboratory and implicated as important mediators of host antimicrobial activity against Gram-negative bacteria (GNB) and as negative regulators of host responses to endotoxin (LPS). The specific aims are (1) to further define the molecular determinants of BPI function, (2) to further characterize the structural and functional properties of the p15s and to identify p15 homologues in other species, and (3) to determine the role and regulation of BPI and p15 function in inflammatory exudates and to characterize BPI-independent antimicrobial activity in inflammatory fluids, Insights gained from this work will likely provide a better understanding of endogenous mechanisms that determine host responses to endotoxin and defense against invading GNB and help in designing specific therapeutic agents for the treatment of invasive GNB infections and endotoxeimia when endogenous defenses and conventional antibiotics are inadequate.

描述(改编自申请人的摘要)：本提案涉及 两个化合物的进一步结构和功能表征 中性粒细胞中的脂多糖结合抗菌蛋白， 杀菌/通透性增加蛋白(BPI)及其15 kDa 蛋白质异构体(P15s)及BPI的作用和调控研究 P15在炎性渗出物中发挥作用。这些蛋白质已经被 在这个实验室中分离和克隆出了一个重要的 革兰氏阴性菌宿主抗菌活性的介体 (GNB)和作为宿主对内毒素(LPS)反应的负调节因子。 具体目标是(1)进一步定义分子决定因素 (2)进一步刻画了BPI函数的结构和性质 P15s的功能性质和鉴定其他 (3)确定BPI和p15的作用和调节 炎性渗出物的功能及BPI非依赖性的特征 炎性液体中的抗菌活性，从中获得的启示 这项工作可能会为更好地理解内源 决定宿主对内毒素反应和防御的机制 防止GNB入侵并帮助设计特定的治疗剂 用于治疗侵袭性巨细胞病毒感染和内毒素血症 内源性防御和常规抗生素是不够的。