Suzuki H, Miura S, Liu Y Y, Tsuchiya M, Ishii H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Peptides. 1995;16(8):1447-52. doi: 10.1016/0196-9781(95)02050-0.
Substance P (SP), one of the established neurotransmitters, evokes an immunoinflammatory response involving leukocyte adhesion to venular endothelium and the degranulation of mast cells. The pathogenetic relationship between these responses, however, remains unresolved. In this study, we propose to examine the changes associated with the activation of mast cells, as well as leukocyte adhesion to venular endothelium by in vivo observation of the rat mesentery. The use of an in vitro assay for intracellular Ca2+ mobilization and the degranulation of mast cells demonstrated the significant upper shift of concentration response to SP (10(-4)-10(-5) M). In vivo experiments on the mesenteric microcirculation also showed that SP induced a significant increase in the number of degranulated mast cells as well as in the number of leukocytes adherent to the venular wall. Tranilast, a mast cell stabilizer, as well as SP antagonist (CP-96,345) significantly attenuated the extent of mast cell degranulation and leukocyte adhesion elicited by SP. Although an immunoneutralization against CD18 by WT-3 significantly attenuated the leukocyte adhesion, it had no influence on the mast cell degranulation after SP superfusion. These separate in vivo observations show that SP induces leukocyte adhesion to the venular endothelium, possibly through the degranulation of mast cells.
P物质（SP）是一种已确定的神经递质，可引发免疫炎症反应，包括白细胞黏附于小静脉内皮以及肥大细胞脱颗粒。然而，这些反应之间的致病关系仍未得到解决。在本研究中，我们建议通过对大鼠肠系膜进行体内观察，来研究与肥大细胞激活以及白细胞黏附于小静脉内皮相关的变化。利用体外检测细胞内Ca2+动员和肥大细胞脱颗粒的方法，证实了对SP（10(-4)-10(-5) M）浓度反应的显著上移。对肠系膜微循环的体内实验还表明，SP可导致脱颗粒肥大细胞数量以及黏附于小静脉壁的白细胞数量显著增加。曲尼司特，一种肥大细胞稳定剂，以及SP拮抗剂（CP-96,345）可显著减弱SP引起的肥大细胞脱颗粒程度和白细胞黏附。尽管WT-3对CD18的免疫中和显著减弱了白细胞黏附，但在SP灌注后对肥大细胞脱颗粒没有影响。这些单独的体内观察结果表明，SP可能通过肥大细胞脱颗粒诱导白细胞黏附于小静脉内皮。
