HUMORAL FACTORS IN INFLAMMATION

过敏性毒素介导痉挛、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。主要目标是 在人类中的配体C5a被认为是中性粒细胞和 单核细胞(巨噬细胞)。其他细胞类型的参与，如 可发生血小板、淋巴细胞、内皮细胞和肥大细胞 作为粒细胞或单核细胞激活的间接结果 和二级调解人的释放。有证据表明C5a 人中性粒细胞上存在约40,000 kDa的受体 表面，并且该膜组件与 1-3nM kD的配体。人的中性粒细胞没有受体 C3a过敏毒素。 这一建议涉及单核细胞上的C5a和C3a受体 (巨噬细胞)。初步证据表明，单核细胞和 人和动物来源的组织巨噬细胞含有C3a和C5a 感受器。使用化学交联技术来可视化 这些膜成分是一种C3a结合蛋白，大约 1000,000 kDa和约40,000 kDa的C5a结合蛋白 都观察到了。我们计划分离这些受体，鉴定 它们在碳水化合物含量和溶解度方面。单一的 将准备免疫试剂来研究细胞的功能属性 巨噬细胞上的C5a受体及其在纯化中的应用 数量足以进行部分序列分析的受体。 从蛋白质序列分析中设计的探针将用于 完成膜组分的分子分析。我们有 观察转化的小鼠巨噬细胞系表达C5a 感受器。当这些细胞系被注射到腹膜内时 在老鼠体内，生长的肿瘤含有大量的 巨噬细胞的C5a受体数量显著增加(即 从所需的膜组件上调)。我们计划利用这一点 在分离和鉴定中的优势发现 巨噬细胞趋化(C5a)受体。一种生物、生化的 单核细胞表面过敏性毒素受体的分子分析 巨噬细胞应该有助于更好地理解其作用 体液因素在调节免疫和炎症中的作用 回应。循环单核细胞和组织巨噬细胞似乎 在宿主防御机制中发挥着举足轻重的作用。中国早期事件 靶细胞激活是由以下因素引起的 过敏性毒素和细菌产品表明它们 代表具有重大生物后果的激活剂。

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.