SUB-EPITHELIAL ANTIGENS

上皮下抗原

• 批准号: 2079097
• 负责人: ROBERT E BURGESON
• 金额: $ 30.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 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 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2079097
• 关键词: artificial skin; basement membrane; biological models; cell adhesion; cell adhesion molecules; epidermolysis bullosa; epithelium; human tissue; intercellular connection; keratinocyte; laboratory mouse; laboratory rabbit; laminin; protein sequence; protein structure function; skin

The anchoring complex is an ultrastructural feature of the dermal-epidermal basement membrane that includes the hemidesmosomes, anchoring filaments and anchoring fibrils. These structures are believed to work as a unit to stabilize epithelial attachment to the underlying basement membrane. Failure of components of the anchoring complex results in spontaneous blistering characteristic of the inherited bullous diseases. We have recently identified two laminin variants that are components of the anchoring filaments. We have termed these kalinin and K-laminin. We know that kalinin is absent from the basement membrane zone of patients with lethal epidermolysis bullosa. Kalinin is a cell adhesion macromolecule specific for certain types of epithelial cells including keratinocytes. For these cells, kalinin substitutes for laminin as the favored growth substrate. Monoclonal antibodies made to kalinin cause cell detachment and de-epithelialization of whole skin in vitro. This application is focused upon continued characterization of the structure and function of kalinin and K-laminin. We propose to isolate kalinin and K-laminin for protein sequence determinations and for preparing protein fragments; to complete the deduced amino acid sequences of these chains and to express selected subdomains in vitro; and to generate domain specific monoclonal antibodies. These reagents will be used to evaluate the binding function of kalinin and K-laminin subdomains. We will interfere with these functions in an in vitro skin equivalent model. These probes will also be used to evaluate mutations in the kalinin and K-laminin chains relative to the pathogenesis of junctional epidermolysis bullosa.

锚定复合物是一个超微结构的特点， 真皮-表皮基底膜，包括半桥粒， 锚定丝和锚定原纤维。 据信这些结构 作为一个整体来稳定上皮附着在 基底膜 锚定复合体组件失效 导致遗传性大疱性疾病的自发性水疱 疾病 我们最近发现了两种层粘连蛋白变体， 锚定细丝的组分。 我们称之为卡利宁， K层粘连蛋白 我们知道在基底膜上没有激肽 致死性大疱性表皮病患者区。 加里宁是一个细胞 对某些类型上皮细胞特异的粘附大分子 包括角质形成细胞。 对于这些细胞，卡林素取代了 层粘连蛋白作为有利的生长基质。 单克隆抗体， 卡林蛋白引起细胞脱离和整个皮肤去上皮化， 体外 本申请的重点是继续表征 kalinin和K-laminin的结构和功能。 我们建议 用于蛋白质序列测定分离的激肽和K-层粘连蛋白， 制备蛋白质片段;完成推导的氨基酸序列 并在体外表达选定的亚结构域;以及 产生结构域特异性单克隆抗体。 这些试剂将 用于评价激肽和K-层粘连蛋白的结合功能 子域。 我们将在体外皮肤中干扰这些功能 等效模型 这些探针也将用于评估突变 在kalinin和K-层粘连蛋白链中与 交界性大疱性表皮