Reactive Intermediates in Leukocyte Systems

白细胞系统中的反应中间体

• 批准号: 8911916
• 负责人: Christopher Foote
• 金额: $ 27.82万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8911916&HistoricalAwards=false
• 关键词: Reactive; Intermediates; Leukocyte; Systems

This project by C. Foote and R. Lehrer of UCLA is within the Chemistry of Life Processes Program, jointly supported by Organic Dynamics of the Chemistry Division and Cell Biology of the Division of Cellular Biosciences. This work deals with the role of white blood cells in the defense against infection. Efforts will be made to learn the details about how oxygen is utilized during this process. The active chlorinating species and other strong oxidants in the antimicrobial action of human polymorphonuclear leukocytes (PMNs), eosinophils and macrophages will be characterized by chemical means. A quantitative trimethoxybenzene assay will be used for the production of hypochlorous acid, and systems will be designed to trap other possible oxidizing species in defined locations in both the interior and exterior of these cells. Reactions of HOCl and other chlorinating agents will be studied to obtain chemical fingerprints for various positive chlorine species "in vitro" and in cells. Although it is likely that HOCl or a similar species is the major oxygen-dependent antimicrobial species of the neutrophil (HOBR in the eosinophil), an unresolved problem is the mechanism by which macrophages (which lack the MPO of PMNs) and MPO-deficient PMNs kill organisms. This mechanism might involve singlet oxygen, other active oxygen species, or something else. Singlet oxygen detection methodology will be further refined, and technology will be developed for the detection of other reactive species to attack this problem. Attempts to detect singlet oxygen quantitatively in eosinophils and further improvements on the halogen assay will be made. Chemical probes for singlet oxygen, halogens, and other species which are covalently bonded to readily-phagocyzed polymer microbeads should provide useful, localizable probes for the white-cell phagocytic vacuole. This should allow an answer to the question of whether all the oxidant is produced within the phagocytic vesicle or whether some escapes to the media.

该项目由C。Foote和R.加州大学洛杉矶分校的莱勒是在 生命过程化学项目，由 有机化学动力学与细胞生物学 细胞生物科学部 这项工作涉及 白色血细胞在抵抗感染中的作用。 将努力学习有关氧气是如何 在这个过程中使用。 活性氯化物种和其他强氧化剂， 人多形核白细胞抗菌作用 中性粒细胞（PMN）、嗜酸性粒细胞和巨噬细胞的特征在于： 化学手段。 将进行三甲氧基苯定量测定。 用于生产次氯酸，系统将 被设计为在限定的环境中捕获其他可能的氧化物质， 在这些细胞的内部和外部的位置。 将研究HOCl和其他氯化剂的反应 以获得各种阳性氯的化学指纹 “在体外”和细胞中。 尽管很可能 HOCl或类似的物质是主要的氧依赖性的 嗜中性粒细胞的抗菌物质（HOBR） 嗜酸性粒细胞），一个尚未解决的问题是机制， 巨噬细胞（缺少PMN的MPO）和MPO缺陷型PMN 杀死有机体。 这种机制可能涉及单线态氧， 其他的活性氧物种，或者其他的东西。 单线态氧 检测方法将进一步完善，技术 将被开发用于检测其他活性物质 来解决这个问题。 探测单线态氧的尝试 在嗜酸性粒细胞中的定量和进一步改善 将进行卤素测定。 单线态化学探针 氧、卤素和其他共价键合的物质 为了易于吞噬聚合物微珠， 白细胞吞噬空泡的可定位探针。 这 应该可以回答是否所有的问题， 氧化剂在吞噬囊泡内产生，或者 有些人逃到了媒体面前。