HUMORAL FACTORS IN INFLAMMATION

过敏毒素介导痉挛，趋化和 免疫调节反应主要通过特异性受体 与粒细胞和单核细胞的相互作用。 主要目标 人的配体C5 a被认为是中性粒细胞， 单核细胞（巨噬细胞）。 其他类型的细胞，如 血小板、淋巴细胞、内皮细胞和肥大细胞 作为粒细胞或单核细胞活化的间接结果 和次级介质释放。 有证据表明，C5 a 约40，000 kDa的受体存在于人嗜中性粒细胞上 表面，并且该膜组分具有对 1-3 nM Kd的配体。 人的中性粒细胞没有受体， C3 a过敏毒素。 该提议涉及单核细胞上的C5 a和C3 a受体两者 （巨噬细胞）。 初步证据表明，单核细胞和 来自人和动物来源的组织巨噬细胞具有C3 a和C5 a 受体。 利用化学交联技术 这些膜成分，C3 a结合蛋白约 1000，000 kDa和约40，000 kDa的C5 a结合蛋白 观察了 我们计划分离这些受体， 它们在碳水化合物含量和溶解度方面。 单特异 将制备免疫试剂以研究 巨噬细胞上的C5 a受体，并用于纯化巨噬细胞上的C5 a受体。 受体的数量足以进行部分序列分析。 根据蛋白质序列分析设计的探针将用于 膜成分的完整分子分析。 我们有 观察到转化的鼠巨噬细胞系表达C5 a， 受体。 当这些细胞系被腹腔注射 在小鼠体内，生长的肿瘤含有大量的 具有显著增加的C5 a受体数量的巨噬细胞（即， 从所需的膜组分上调）。 我们计划用这个 发现有利于分离和表征 巨噬细胞趋化性（C5 a）受体。 一种生物的，生化的 单核细胞上过敏毒素受体的分子分析 和巨噬细胞的作用， 体液因子在调节免疫和炎症中起作用， 应答 循环单核细胞和组织巨噬细胞似乎 在宿主防御机制中起着关键作用。 中的早期事件 靶细胞活化由以下因素引起 过敏毒素和细菌产物，表明它们 代表主要生物学后果的激活剂。

The anaphylatoxins mediate spasmogenic, chemotactic and immunoregulatory responses primarily through specific receptor interactions with granulocytes and monocytes. The primary targets of the ligand C5a in man are believed to be the neutrophil and the monocyte (macrophage). Involvement of other cell types such as platelets, lymphocytes, endothelial cells and mast cells may occur as an indirect consequence of granulocyte or monocyte activation and secondary mediator release. Evidence exists that a C5a receptor of approximately 40,000 kDa occurs on the human neutrophil surface and that this membrane component has an affinity for the ligand of 1-3 nM Kd. The human neutrophil has no receptor for the C3a anaphylatoxin. This proposal concerns both C5a and C3a receptors on monocytes (macrophages). Preliminary evidence indicates that monocytes and tissue macrophages from human and animal sources have C3a and C5a receptors. Using chemical cross-linking techniques to visualize these membrane components, a C3a binding protein of approximately 1000,000 kDa and a C5a binding protein of approximately 40,000 kDa were observed. We plan to isolate these receptors, characterize them in terms of carbohydrate content and solubility. Monospecific immune reagents will be prepared to study functional attributes of the C5a receptor on macrophages and for use in purification of the receptor in quantities adequate for partial sequence analysis. Probes designed from protein sequence analysis will be used for complete molecular analysis of the membrane component. We have observed that transformed murine macrophage cell lines express C5a receptors. When these cell lines are injected intraperitoneally into mice, tumors are grown that contain large quantities of the macrophages having markedly enhanced number of C5a receptors (i.e. upregulated from membrane components desired). We plan to use this discovery to advantage in isolation and characterization of the macrophage chemotactic (C5a) receptor. A biologic, biochemical and molecular analysis of the anaphylatoxic receptors on monocytes and macrophages should lead to a better understanding of the role that humoral factors play in modulating immune and inflammatory responses. Circulating monocytes and tissue macrophages appear to play a pivotal role in host defense mechanisms. Early events in target cell activation are elicited by factors such as anaphylatoxins and bacterial products indicating that they represent activators of major biologic consequence.