HUMAN DERMAL ENDOTHELIAL CELLS IN SKIN DISEASE

人真皮微血管内皮细胞(HDMEC) 定位于在皮肤炎症反应中发挥重要作用。 由于在纯培养中培养这些细胞很困难，几乎没有 已知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出纯HDMEC 包皮。这些HDMEC可以扩展为大细胞数并用于 功能研究。此外，这个实验室最近成功地 诱导人脐静脉内皮细胞(HUVE)和人脐静脉内皮细胞 在体外经历极快的分化。差异化的 内皮细胞变得细长，形成管状的管腔，类似于 体内的微血管。我们将系统地研究它的作用 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。在这方面的研究 该提案将描述与免疫相关的细胞表面 受体和抗原，以及细胞黏附分子存在于 差异化和未差异化的HDMEC，以便深入了解 这些细胞的潜在免疫功能。的能力 诱导或调节这些基因表达的生物反应修饰物 分子将被精确地定义。这项提案将评估 纯化的人T淋巴细胞和单核细胞与未分化的T细胞结合 并通过分化HDMEC和HUVE来阐明白细胞的作用机制。 内皮细胞相互作用。结合的T细胞亚群将 也被定义为。此外，细胞黏附分子负责 T细胞和单核细胞对HDMEC的黏附将使用特定的 针对T细胞、单核细胞和内皮细胞的单抗 细胞黏附分子。常用的治疗方法的能力 方式，如皮质类固醇，和紫外线影响 细胞黏附分子的表达和细胞与细胞的黏附 系统评估。本提案中的相关研究将利用 细胞毒性试验评估抗内皮细胞的存在 皮肤和/或系统性脉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 将被免疫沉淀并进行免疫化学分析。因此， 这项提案中的研究将为 皮肤炎的发生和发展与其直接相关 炎症性皮肤病的病理生理学研究。

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.