Matis W L, Lavker R M, Murphy G F
Department of Dermatology, University of Pennsylvania, Philadelphia.
J Invest Dermatol. 1990 Apr;94(4):492-5. doi: 10.1111/1523-1747.ep12874665.
Leukocyte trafficking in normal and diseased skin appears to be initially governed by endothelial surface glycoproteins that promote adhesive interactions with circulating leukocytes. In a separate study, we have demonstrated that one of these glycoproteins, endothelial-leukocyte adhesion molecule-1 (ELAM-1), is rapidly induced on postcapillary dermal venules as a direct consequence of experimentally-elicited degranulation of adjacent mast cells (Proc Natl Acad Sci USA 86:8972-8976, 1989). A principle endogenous mediator of mast cell degranulation is the neuropeptide substance P. In this study, we exposed organ cultures of neonatal human foreskins for 45 min to substance P or to a substance P analogue (D-pro4, D-trp7,9)SP(4-11) that binds to the identical mast cell surface receptor but which does not provoke histamine release. Dermal mast cells were uniformly degranulated only in explants exposed to substance P, as judged by ultrastructural analysis. After subsequent culture in medium alone for 6 h, superficial venules of explants exposed to substance P showed evidence of ELAM-1 induction, as documented histochemically using H4/18 monoclonal antibody. ELAM-1 was not induced by substance P analogue. Furthermore, preincubation of explants with analogue or with the mast cell inhibitor, cromolyn sodium, abrogated the ability of substance P to induce ELAM-1. From these results we suggest that substance P endogenously released by dermal nerve fibers upon physiologic or electrical stimulation may be important in the regulation of endothelial-leukocyte interactions in vivo. This concept provides further evidence for a neurogenic and psychogenic modulation of the immune response, and may be relevant to the course of naturally occurring dermatoses (e.g., psoriasis) that are commonly exacerbated by emotional stress.
在正常皮肤和病变皮肤中，白细胞的迁移最初似乎受内皮表面糖蛋白的调控，这些糖蛋白促进与循环白细胞的黏附相互作用。在另一项研究中，我们已证明这些糖蛋白之一，即内皮细胞白细胞黏附分子-1（ELAM-1），在实验诱导相邻肥大细胞脱颗粒后，后毛细血管真皮小静脉上会迅速被诱导产生（《美国国家科学院院刊》86:8972 - 8976, 1989）。肥大细胞脱颗粒的一种主要内源性介质是神经肽P物质。在本研究中，我们将新生儿人包皮的器官培养物暴露于P物质或一种与相同肥大细胞表面受体结合但不引发组胺释放的P物质类似物（D-pro4, D-trp7,9）SP(4 - 11) 45分钟。通过超微结构分析判断，仅在暴露于P物质的外植体中，真皮肥大细胞均匀地发生了脱颗粒。在随后仅在培养基中培养6小时后，暴露于P物质的外植体的浅表小静脉显示出ELAM-1诱导的证据，这是使用H4/18单克隆抗体通过组织化学记录的。P物质类似物未诱导ELAM-1。此外，用类似物或肥大细胞抑制剂色甘酸钠对外植体进行预孵育，消除了P物质诱导ELAM-1的能力。从这些结果我们推测，在生理或电刺激下由真皮神经纤维内源性释放的P物质可能在体内内皮细胞与白细胞相互作用的调节中起重要作用。这一概念为免疫反应的神经源性和精神源性调节提供了进一步的证据，并且可能与通常因情绪压力而加重的自然发生的皮肤病（如银屑病）的病程相关。
