RECEPTOR FUNCTION ON HUMAN MONOCYTE/MACROPHAGES

描述(摘自申请者摘要)：单核/巨噬细胞 炎症反应的关键要素。单核细胞从 外周循环，并进入血管外区域 细胞外结缔组织基质。在这种环境下，单核细胞 摄取并杀死入侵的病原体。致病性革兰氏阳性和革兰氏阳性 阴性细菌需要调理作用才能被识别、吞噬和 被单核/巨噬细胞杀死。通过以下方式激活补体系统 这些微生物会引发炎症反应，从而导致 血清调理蛋白C3b、Ic3b和Ig G在细菌上的沉积 浮出水面。它们与之调理的特定质膜受体 细菌结合(分别为CR1、CR3和FCR)已被鉴定，并 具有结构特征的。体外和体内研究表明， 通过FCR的吞噬作用是吞噬细胞的一种结构性特征， CR1和CR3介导的吞噬作用受发育调控。 这项研究计划的总体目标是了解 单核/巨噬细胞的细菌活性在 发炎。因此，他建议研究细胞外的调节。 结缔组织基质、补体成分和细胞因子 单核细胞对调理细菌的杀菌活性。该项目已 三个具体目标：1)确定CR1、CR3和FCR在 单核细胞介导对调理细菌的吞噬和杀灭作用 黏附于I型胶原胶；2)通过 哪种I型胶原胶黏附激活单核细胞补体 吞噬的受体；3)定量吞噬和 单核细胞与结缔组织基质黏附的杀菌活性 由纤维连接蛋白、层粘连蛋白和玻璃体连接蛋白在胶原中混合而成 凝胶；确定补体的额外调节作用 在这种环境中，成分和细胞因子对吞噬细胞功能的影响 确定吞噬细胞功能的调节是否通过 补体受体和FCR功能的调节，或通过激活 呼吸爆发了。

DESCRIPTION (Adapted from applicant's abstract): Monocyte/macrophages are critical elements of the inflammatory response. Monocytes emigrate from the peripheral circulation and enter into an extravascular region of extracellular connective tissue matrices. In this milieu, monocytes ingest and kill invading pathogens. Pathogenic Gram-positive and Gram- negative bacteria require opsonization to be recognized, phagocytized and killed by monocyte/macrophages. Activation of the complement system by these microorganism initiates the inflammatory response, that results in the deposition of the serum opsonins C3b, iC3b, and IgG on the bacterial surface. The specific plasma membrane receptors to which these opsonized bacteria bind, (CR1, CR3, and FcR, respectively) have been identified and structurally characterized. In vitro and in vivo studies have shown that phagocytosis via FcR is a constitutive property of phagocytes and that CR1- and CR3-mediated phagocytosis is regulated developmentally. The overall goal of this research proposal is to understand how monocyte/macrophage bactericial activity is regulated at sites of inflammation. Therefore, he proposes to study regulation by extracellular connective tissue matrices, complement components, and cytokines of monocyte bactericidal activity for opsonized bacteria. The project has three specific aims: 1) to determine the roles of CR1, CR3, and FcR in mediating the phagocytosis and killing of opsonized bacteria by monocytes adherent to type I collagen gels; 2) to investigate the mechanism by which adherence to type I collagen gels activates monocyte complement receptors for phagocytosis; 3) to quantify the phagocytic and bactericidal activity of monocytes adherent to connective tissue matrices formed from mixtures of fibronectin, laminin, and vitronectin in collagen gels; to determine the additional regulatory effects of complement components and cytokines on phagocyte function in this milieu; and to determine if modulation of phagocyte function is mediated through regulation of complement receptor and FcR function, or by activation of the respiratory burst.