NEURO MICROVASCULAR MECHANISMS IN SKIN INFLAMMATION

描述：（改编自申请人的摘要）长期 该应用程序的目标是定义负责 皮肤神经源性炎症的起始和终止，以及 确定这些过程中的缺陷是否会导致炎症反应失调， 皮肤的反应。 需要检验的主要假设是：（1） 神经系统可以通过释放 神经肽（例如，P物质（SP））能够直接起作用 在真皮微血管系统上介导血浆外渗、内皮 细胞粘附分子表达、内皮间隙形成和中性粒细胞 浸润，和（2）这些促炎活性减弱 通过特定的细胞表面蛋白酶和脱敏的 靶内皮细胞上的相应神经肽受体。 有 三个具体目标。 首先是表征SP与 真皮微血管内皮细胞（DMEC）上的受体和光谱 DMEC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。 第三是确定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，刺激性 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.