STRUCTURE AND FUNCTION OF HUMAN SECRETORY COMPONENT

分泌成分(SC)在粘膜免疫中起着核心作用 系统。它的功能是跨细胞的间隔膜受体。 转运蛋白及其配体聚合体IgA的酶抑制物。一块嵌板 人类干细胞的单抗，在我们的实验室中得到了鉴定， 为研究SC的免疫生物学提供了一个独特的机会。我们的基础 目标是检查使SC能够 在其多重专业角色中发挥作用。临床研究将寻求 不同组织中SC大小和结构不均匀的证据 以及来自不同个体的分泌物。这些研究可能会提供 供应链调节作用的证据和对供应链变化的洞察 恶性上皮细胞的代谢。 各种分泌物中的干细胞将通过免疫亲和力分离出来 层析和某些制剂将通过脱糖作用进行修饰 以及有限的和酶促的蛋白质分解。最初的十二烷基硫酸钠-聚丙烯酰胺凝胶 将使用电泳法、高效液相色谱法和与单抗的反应。 表征产物的大小和表位结构。 随后，氨基酸和碳水化合物的组成和氨基酸 将对某些SC片段进行序列分析。入内 SC制剂的体外功能将通过评估 聚合型IgA结合和抑制IgA蛋白降解。细胞内 这些事件将使用结肠癌来源的细胞系进行检测。这个 SC的细胞内途径将通过免疫细胞化学的方式进行 区分不同物理形式的SC的单抗。 衣霉素将抑制糖基化，注意力集中在 碳水化合物在干细胞功能中的作用。 人抗SC抗体将被用来探测体内构象 通过比较SC的抗体谱来确定SC的受体形式 个体的血清和分泌物。在这些方面起到了调节作用 抗体将在干细胞功能的体外模型中进行测试。 对供应链正常结构和功能的界定将增强我们的 对粘膜免疫及其调控的认识。治疗性的 这一知识的应用可以包括开发用于 以主动或被动免疫或其他治疗剂为靶点 粘膜感染的部位。拟议的研究也可能阐明 恶性上皮细胞中SC代谢的变化可能允许 选择性地使用细胞毒或化疗药物的方向 肿瘤。

Secretory component (SC) plays a central role in the mucosal immune system. It functions as an intergal membrane receptor, transcellular transporter, and protease inhibitor for its ligand polymeric IgA. A panel of monoclonal antibodies to human SC, characterized in our laboratories, offers a unique opportunity to study the immunobiology of SC. Our basic objective is to examine the structural characteristics which allow SC to function in its multiple specialized roles. Clinical studies will seek evidence for heterogeneity in size and structure of SC in different secretions and from different individuals. These studies may provide evidence for a modulatory role for SC and insight into alterations in SC metabolism in malignant epithelial cells. The SC from various secretions will be isolated by immunoaffinity chromatography and certain preparations will be modified by deglycosylation and limited and enzymatic proteolysis. Initially SDS polyacrylamide gel electrophoresis, HPLC and reaction with monoclonal antibodies will be used to characterize the size and epitopic structure of the products. Subsequently, amino acid and carbohydrate composition and amino acid sequence analysis will be determined for certain SC fragments. The in vitro function of the SC preparations will be assessed by evaluating polymeric IgA binding and inhibition of IgA proteolysis. Intracellular events will be examined using a colon carcinoma derived cell line. The intracellular pathway of SC will be followed by immunocytochemistry using monoclonal antibodies which distinguish the various physical forms of SC. Glycosylation will be inhibited with tunicamycin and attention focused on the role of carbohydrate in SC cellular function. Human IgG antibodies to SC will be used to probe the in vivo conformation of the receptor form of SC by comparing the spectrum of antibodies in the serum and secretions of individuals. A modulatory role for these antibodies will be tested in an in vitro model of SC function. Deliniation of the normal structure and function of SC will enhance our understanding of mucosal immunity and its control. Therapeutic applications of this knowledge may include the development of methods for targeting active or passive immunity or other therapeutic agents to the site of mucosal infections. The proposed studies may also elucidate alterations in SC metabolism in malignant epithelial cells which may allow direction of cytotoxic or chemotherapeutic agent selectively to these tumors.