HUMAN DERMAL ENDOTHELIAL CELLS IN SKIN DISEASE

人真皮微血管内皮细胞（HDMEC）是 在皮肤炎症反应中起重要作用。 由于这些细胞在纯培养中生长困难， 了解它们在炎症性皮肤病中的作用。 这个实验室 最近成功地从新生儿中分离和培养了纯HDMEC 包皮 这些HDMEC可以扩展到大的细胞数量，并用于 功能研究。 此外，该实验室最近还成功地 诱导人脐静脉内皮细胞（HUVE）和HDMEC， 在体外经历极其快速的分化。 差异化 内皮细胞变长并形成管腔， 体内微血管 我们将系统地研究 微血管内皮细胞在皮肤炎症中的作用 诱导内皮细胞分化的信号。 研究的 该提案将表征免疫相关细胞表面 受体和抗原，以及存在于 分化和未分化的HDMEC，以便深入了解 这些细胞的潜在免疫功能。 的能力 生物反应调节剂，以诱导或调节这些 分子将被精确定义。 该提案将评估 纯化的人T淋巴细胞和单核细胞结合未分化的 并对HDMEC和HUVE进行分化，以阐明白细胞- 内皮细胞相互作用 结合的T细胞亚群将 也被定义。 此外，细胞粘附分子负责 T细胞和单核细胞对HDMEC的粘附将使用特定的 针对T细胞、单核细胞和内皮细胞的单克隆抗体 细胞粘附分子 常用治疗药物的能力 如皮质类固醇和紫外线等方式来影响 细胞粘附分子的表达和细胞-细胞粘附将是 系统评估。 本提案中的相关研究将利用 细胞毒性试验，以评估抗内皮细胞的存在 皮肤和/或系统性血管炎患者血清中的抗体。 抗内皮细胞抗体结合的细胞表面分子 进行免疫沉淀和免疫化学分析。 因此 本提案中的研究将为以下方面提供新的重要见解： 皮肤炎症的发生和发展， 炎症性皮肤病的病理生理学

Human dermal microvascular endothelial cells (HDMEC) are strategically located to play an important role in the cutaneous inflammatory response. Because of the difficult in growing these cells in pure culture, little is known about their functions in inflammatory skin diseases. This laboratory has recently succeeded in isolating and culturing pure HDMEC from neonatal foreskins. These HDMEC can be expanded to large cell numbers and used in functional studies. In addition, this laboratory recently succeeded in inducing both human umbilical vein endothelial cells (HUVE) and HDMEC to undergo extremely rapid differentiation in vitro. The differentiated endothelial cells become elongated and form tubes with lumina that resemble microvessels in vivo. We will systematically study the role of microvascular endothelial cells in cutaneous inflammation and define the signals that induce endothelial cell differentiation. Studies in this proposal will characterize the immunologically relevant cell surface receptors and antigens, as well as cell adhesion molecules present on differentiated and undifferentiated HDMEC, in order to gain insights into the potential immunologic functions of these cells. The ability of biologic response modifiers to induce or modulate the expression of these molecules will be precisely defined. This proposal will assess the ability of purified human T-lymphocytes and monocytes to bind to undifferentiated and differentiated HDMEC and HUVE to delineate the mechanisms of leukocyte- endothelial cell interaction. The subpopulations of T-cells that bind will also be defined. In addition, the cell adhesion molecules responsible for T-cell and monocyte adherence to HDMEC will be defined using specific monoclonal antibodies directed against T-cell, monocyte, and endothelial cell adherence molecules. The ability of commonly used therapeutic modalities such as corticosteroids, and ultraviolet light to affect expression of cell adhesion molecules and cell-cell adherence will be systematically assessed. Related studies in this proposal will utilize cytotoxicity assays to assess the presence of antiendothelial cell antibodies in sera of patients with cutaneous and/or systemic vasculitis. The cell surface molecules bound by the antiendothelial cell antibodies will be immunoprecipitated and analyzed immunochemically. Thus, the studies in this proposal will provide new and important insights into the initiation and evolution of cutaneous inflammation and have direct bearing on the pathophysiology of inflammatory skin diseases.