MECHANISM OF HUMAN LEUKOCYTE CHEMOTAXIS

拟议研究的长期目标是确定 人中性粒细胞趋化功能丧失的机制 与热损伤和腹内感染的关系 确定可以恢复趋化功能或防止其 损失。本申请的具体目的包括：(1)补充 可用于包括多孔室膜的实验室方法 过滤技术，加入三种或三种化学吸引剂，以更好地考虑 患者中性粒细胞趋化功能丧失的广度，并发展 方法鉴定和物理分离中性粒细胞亚群； (2)继续我们对患者中性粒细胞趋化功能障碍的研究 证实我们的初步观察，补体级联被激活 在热损伤后以及在感染和暴露期间血浆中 中性粒细胞对补体激活产物的作用是部分原因 对于丧失趋化迁移功能；(3)继续我们的研究 控制中性粒细胞以确定在体外治疗条件下 兼具随机性和趋化性迁移功能，验证其作用 氧代谢产物在随机运动性丧失和模型缺陷中的作用 确定患者中性粒细胞趋化功能；以及(4)开始 考虑患者中性粒细胞的体外条件或治疗 恢复趋化功能。 宿主对感染的防御涉及几种类型的吞噬细胞和 这些细胞的多种细胞活性与杀灭微生物有关 功能。中性粒细胞趋化功能是必不可少的首要作用 这些细胞在宿主防御感染中的作用。有很多证据表明 来证明仅是运动能力受损就足以影响 主机的防御是不利的。除了几种遗传性疾病 中性粒细胞迁移功能、中性粒细胞丢失机制的研究 其他情况下的趋化功能仍然知之甚少。我们 期望通过本文件中描述的实验生成的信息 应用将增加我们对损失机制的理解。 中性粒细胞在烫伤和感染中的趋化作用。 所获得的信息也将适用于识别 在这些情况下预防趋化功能障碍的治疗，以 了解单核细胞和巨噬细胞的迁移功能，并为 补体激活的体内研究背景及补体的作用 补体激活产物在免疫功能调节中的作用 感染和癌症。

The long term objectives of the proposed research are to identify mechanisms of loss of human neutrophil chemotactic function which occurs in association with thermal injury and intra-abdominal infection and to identify treatments which will restore chemotactic function or prevent its loss. Specific aims in this application include: (1) supplementation of laboratory methods available to include the multiwell chamber membrane filter technique, to add three or chemoattractants to better consider the breadth of loss of patient neutrophil chemotactic function, and to develop methods to identify and physically isolate subpopulations of neutrophils; (2) continue our studies of patient neutrophil chemotactic dysfunction to verify our preliminary observation that the complement cascade is activated in plasma following thermal injury and during infection and that exposure of neutrophils to products of complement activation is in part responsible for loss of chemotactic migratory function; (3) continue our studies of control neutrophils to identify in vitro treatment conditions which alter both random and chemotactic migratory functions, to verify the role of oxygen metabolites in loss of random motility, and to model defects identified for patient neutrophil chemotactic function; and (4) to begin to consider in vitro conditions or treatments of patient neutrophils which restore chemotactic function. Host defense against infection involves several types of phagocytes and multiple cellular activities of these cells related to microbicidal function. Neutrophil chemotactic function is essential to the primary role of these cells in host defense against infection. There is much evidence to demonstrate that impaired motility alone may be sufficient to affect host defenses adversely. With the exception of several inherited disorders of neutrophil migratory function, mechanisms of loss of neutrophil chemotactic function in other situations remain poorly understood. We expect that information generated from experiments described in this application will add to our understanding of mechanisms of loss of neutrophil chemotactic function in thermal injury and infection. Information obtained will also have application to identification of treatments to prevent chemotactic dysfunction in these situations, to understanding monocyte and macraphage migratory functions, and to providing background for studies of complement activation in vivo and the role of products of complement activation in modulation of immune function in infection and cancer.