CHARACTERIZATION OF SUB-EPITHELIAL MATRIX ANTIGENS

上皮下基质抗原的表征

• 批准号: 3157343
• 负责人: ROBERT E BURGESON
• 金额: $ 6.41万
• 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/3157343
• 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.

外部鳞状上皮下方的基底膜区 组织的超微结构比基底膜区域更复杂 其他组织。 除了致密层之外，这些区域还包含 其他细胞元件，例如基底细胞的半桥粒， 半桥粒和致密层之间的锚定丝， 锚定原纤维似乎将致密层与 底层结缔组织和氧化纤维可能介导 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松解症影响特定成分 该区域，并向外部展示这些结构的独特性 组织。 作为描述参与该过程的分子网络的第一次尝试 上皮细胞与底层分子的相互作用 矩阵，我们已经生产了尚未识别的单克隆抗体 成分。 其中两种抗体已被选择用于进一步 表征。 其中之一具有免疫学和生化 特性与锚定细丝的预期特性相似。 这 其他具有类似于氧化钛纤维的特性。 我们已经证明 这些抗原由特定细胞群合成，并具有 证明了其化学表征的可行性。 我们 建议详细分离和表征这些抗原，以鉴定 具有超微结构观察到的纤维成分的抗原 基底膜区，并研究之间的潜在相互作用 这些成分和其他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 关于这些基底膜区域蛋白，将有助于形成基础 为了了解这个独特区域的结构。 这 信息将为形成以下假设提供背景 大疱性表皮松解症发病机制的分子事件 和大疱性类天疱疮。