CHARACTERIZATION OF SUB-EPITHELIAL MATRIX ANTIGENS

上皮下基质抗原的表征

• 批准号: 3157342
• 负责人: ROBERT E BURGESON
• 金额: $ 5.71万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-23 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3157342
• 关键词: antibody; basement membrane; electron microscopy; enzyme linked immunosorbent assay; epidermolysis bullosa; epithelium; extracellular matrix; fibroblasts; gel electrophoresis; human tissue; immunofluorescence technique; monoclonal antibody; skin; skin disorder; surface antigens; tissue /cell culture

The basement membrane zone underlying the squamous epithelium of external tissues is ultrastructurally more complex than basement membrane zones of other tissues. In addition to lamina densa, these regions contain additional cellular elements such as the hemidesmosomes of the basal cells, anchoring filaments between the hemidesmosomes and the lamina densa, anchoring fibrils which appear to connect the lamina densa with the underlying connective tissue, and oxytalan fibers which may mediate the interaction of elastic elements with the lamina densa. The diseases of bullous pemphigoid and epidermolysis bullosa affect specific components in this region, and demonstrate the uniqueness of these structures to external tissues. As a first attempt to describe the network of molecules involved in the interaction of epithelial cells with molecules deep in the underlying matrix, we have produced monoclonal antibodies to yet unrecognized components. Two of these antibodies have been selected for further characterization. One of them have immunological and biochemical characteristics similar to those expected for anchoring filaments. The other has characteristics resembling oxytalan fibers. We have shown that these antigens are synthesized by specific cell populations and have demonstrated the feasibility of their chemical characterization. We propose to isolate and characterize these antigens in detail, to identify the antigen with ultrastructurally observed fibrous components of the basement membrane zone, and to investigate potential interactions between these components and other known connective tissue elements. We anticipate that the proposed studies will provide specific information regarding these basement membrane zone proteins and will help form a basis for the understanding of the structure of this unique region. This information will provide the background for forming hypotheses regarding the molecular events underlying the pathogenesis of epidermolysis bullosa and bullous pemphigoid.

基底膜区位于外表皮鳞状上皮之下， 组织在超微结构上比基底膜区更复杂， 其他组织。 除了致密层，这些区域还含有 另外的细胞成分如基底细胞的半桥粒， 在半桥粒和致密板之间的锚定丝， 锚定纤维似乎连接致密层与 下面的结缔组织，和oxytalan纤维，可能介导 弹性元件与致密层的相互作用。 的疾病 大疱性类天疱疮和大疱性表皮病影响 这一地区，并证明这些结构的独特性，以外部 组织中 作为首次尝试描述参与的分子网络， 上皮细胞与底层分子的相互作用 基质，我们已经产生了单克隆抗体， 件. 这些抗体中的两种已被选择用于进一步的研究。 特征化 其中一种具有免疫学和生化学 这些特性类似于锚定细丝所预期的那些特性。 的 另一种具有类似Oxytalan纤维的特征。 我们已经证明 这些抗原由特定的细胞群合成， 证明了其化学表征的可行性。 我们 建议分离和详细描述这些抗原，以鉴定 抗原与超微结构观察到的纤维成分的 基底膜区，并研究潜在的相互作用， 这些成分和其它已知的结缔组织成分。 我们预计，拟议的研究将提供具体信息， 关于这些基底膜区蛋白质，将有助于形成一个基础， 来了解这个独特区域的结构。 这 信息将提供形成假设的背景， 大疱性表皮病发病机制的分子事件 和大疱性类天疱疮