RECEPTOR FUNCTION ON HUMAN MONOCYTE/MACROPHAGES

描述（改编自申请人摘要）：单核细胞/巨噬细胞是 炎症反应的关键因素。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 在这种环境中，单核细胞 吞噬并杀死入侵的病原体 致病性革兰氏阳性和革兰氏- 阴性细菌需要调理素作用来识别、吞噬并 被单核细胞/巨噬细胞杀死。 补体系统的激活 这些微生物会引发炎症反应， 血清调理素C3 b、iC 3b和IgG在细菌上的沉积 面这些细胞所调理的特定质膜受体 细菌结合，（分别为CR 1，CR 3和FcR）已被确定， 结构特征。体外和体内研究表明， 通过FcR的吞噬作用是吞噬细胞的组成性质， CR 1和CR 3介导的吞噬作用是发育调节的。 这项研究的总体目标是了解如何 单核细胞/巨噬细胞的吞噬活性在以下部位受到调节： 炎症因此，他建议研究细胞外 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 三个具体目标：1）确定CR 1，CR 3和FcR在 介导单核细胞对调理细菌的吞噬和杀伤 粘附于I型胶原凝胶; 2）通过以下研究机制： 粘附在I型胶原凝胶上激活单核细胞补体 受体的吞噬作用; 3）量化吞噬和 粘附于结缔组织基质的单核细胞的杀菌活性 由胶原中的纤维连接蛋白、层粘连蛋白和玻连蛋白的混合物形成 凝胶;以确定补体的额外调节作用 成分和细胞因子对该环境中吞噬细胞功能的影响; 确定吞噬细胞功能的调节是否通过 调节补体受体和FcR功能，或通过激活 呼吸爆发

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.