MICROBICIDAL ACTIVITY OF LEUKOCYTES--ACTIVE FACTORS

描述（改编自申请人摘要）：本提案涉及 进一步的结构和功能表征的两个 脂多糖（LPS）结合的抗菌蛋白， 杀菌/通透性增加蛋白（BPI）和15 kDa 蛋白质亚型（p15），以及BPI的作用和调节的研究 和p15在炎性渗出物中的功能。这些蛋白质 在这个实验室里分离和克隆， 宿主抗革兰氏阴性菌抗菌活性介质 (GNB)和作为宿主对内毒素（LPS）反应的负调节剂。 具体目的是：（1）进一步确定分子决定簇 （2）进一步表征了BPI函数的结构和 p15的功能特性，并在其他细胞中鉴定p15同源物， BPI和p15的作用和调控 在炎性渗出物中的作用，并表征BPI非依赖性 炎症液体中的抗微生物活性， 这项工作可能会提供一个更好的理解内源性 决定宿主对内毒素和防御反应的机制 对抗入侵的巨人银行，并帮助设计特定的治疗药物， 用于治疗侵袭性GNB感染和内毒素血症， 内源性防御和常规抗生素是不够的。

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.