NEURO MICROVASCULAR MECHANISMS IN SKIN INFLAMMATION

描述：(改编自申请人的摘要)长期 本申请的目标是定义负责以下各项的机制 皮肤神经源性炎症的开始和结束，以及 确定这些过程中的缺陷是否会导致失调的炎症 皮肤的反应。需要检验的关键假设是：(1) 神经系统可能通过释放激素来调节皮肤炎症 能够直接作用的神经肽(如P物质(SP)) 在真皮微血管系统中调节血浆外渗、内皮 细胞黏附分子表达、内皮细胞间隙形成与中性粒细胞 渗透，以及(2)这些促炎活性减弱 通过特定的细胞表面蛋白水解酶和脱敏的 靶血管内皮细胞上分别有神经肽受体。确实有 三个具体目标。首先是描述SP与 真皮微血管内皮细胞上的受体及其光谱 DMEC因此而介导的促炎过程 神经肽刺激。第二是研究细胞机制。 负责调节DMEC介导的神经源性炎症过程。 第三，确定DMEC介导的神经源性炎症在 过敏性接触性皮炎动物模型的发病机制 皮炎和急性光性皮炎。

DESCRIPTION: (Adapted from the applicant's abstract) The long-term objective of this application is to define the mechanisms responsible for the initiation and termination of cutaneous neurogenic inflammation, and to determine if defects in these processes result in dysregulated inflammatory responses in skin. The key hypotheses to be tested are: (1) That the neurological system may modulate inflammation in skin by releasing neuropeptides (e.g., substance P (SP)) that are capable of directly acting on the dermal microvasculature to mediate plasma extravasation, endothelial cell adhesion molecule expression, endothelial gap formation, and neutrophil infiltration, and (2) that these pro-inflammatory activities are attenuated by specific cell-surface proteases and by the desensitization of the respective neuropeptide receptor on the target endothelial cells. There are three specific aims. First is to characterize the interaction of SP with receptors on dermal microvascular endothelial cells (DMEC) and the spectrum of pro-inflammatory processes mediated by DMEC as a result of this neuropeptide stimulation. Second is to examine the cellular mechanisms responsible for regulating DMEC-mediated neurogenic inflammatory processes. Third is to determine the role of DMEC-mediated neurogenic inflammation in the pathogenesis of animal models of allergic contact dermatitis, irritant dermatitis, and acute photodermatitis.