Smith C H, Barker J N, Morris R W, MacDonald D M, Lee T H
Department of Public Health Medicine, United Medical School, London.
J Immunol. 1993 Sep 15;151(6):3274-82.
Inflammatory cell infiltrates and cell adhesion molecule expression have been examined in normal human skin after intradermal injection of sensory neuropeptides substance P (n = 6), vasoactive intestinal polypeptide (n = 6), and calcitonin gene-related peptide (n = 6) together with PBS as control (n = 4). Each neuropeptide induced rapid, time-dependent neutrophil influx into dermis, which was initially observed at 15 min and persisted for 8 h after injection. Increases in numbers of neutrophils with time after substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide were highly significant when compared with controls p < 0.005, p < 0.005, p < 0.005, respectively (analysis of variance). Substance P additionally induced marked eosinophilic accumulation at 4 and 8 h in four of six subjects. These changes paralleled rapid translocation of P-selectin from cytoplasmic Weibel-Palade granules to luminal membranes by 15 min, and significant up-regulation of E-selectin expression at 4 and 8 h. Increases in percentage of E-selectin positive vessels with respect to time after each neuropeptide were highly significant when compared with controls, p < 0.005, p < 0.005, p < 0.005 (ANOVA), respectively, and were significantly correlated with neutrophil infiltrates, r = 0.55, p < 0.001. VCAM-1 was not expressed, and constitutive ICAM-1 expression on dermal endothelium was unchanged at all time points examined (0-8 h). Induction of endothelial adhesion molecule expression by neuropeptides provides a mechanism for neutrophil accumulation in neurogenic inflammation. Substance P-induced eosinophil accumulation in the absence of VCAM-1 expression suggests that mechanisms distinct from VCAM-1/very late antigen-4 binding mediate selective tissue eosinophilia.
在正常人体皮肤皮内注射感觉神经肽P物质（n = 6）、血管活性肠肽（n = 6）和降钙素基因相关肽（n = 6），并以PBS作为对照（n = 4）后，对炎症细胞浸润和细胞黏附分子表达进行了检测。每种神经肽均诱导中性粒细胞迅速、呈时间依赖性地流入真皮，注射后15分钟开始观察到这种现象，并持续8小时。与对照组相比，P物质、血管活性肠肽和降钙素基因相关肽作用后中性粒细胞数量随时间增加具有高度显著性差异，p分别< 0.005、p < 0.005、p < 0.005（方差分析）。在6名受试者中的4名中，P物质在4小时和8小时还额外诱导了明显的嗜酸性粒细胞聚集。这些变化与P选择素在15分钟内从细胞质Weibel-Palade颗粒迅速转运至管腔膜平行，且在4小时和8小时E选择素表达显著上调。与对照组相比，每种神经肽作用后E选择素阳性血管百分比随时间增加具有高度显著性差异，p分别< 0.005、p < 0.005、p < 0.005（方差分析），且与中性粒细胞浸润显著相关，r = 0.55，p < 0.001。未检测到血管细胞黏附分子-1（VCAM-1）表达，在所有检测时间点（0 - 8小时），真皮内皮细胞组成性细胞间黏附分子-1（ICAM-1）表达均未改变。神经肽诱导内皮细胞黏附分子表达为中性粒细胞在神经源性炎症中的聚集提供了一种机制。在未表达VCAM-1的情况下，P物质诱导嗜酸性粒细胞聚集表明，不同于VCAM-1/极迟抗原-4结合的机制介导了选择性组织嗜酸性粒细胞增多。
