Yancey K B, Bielory L, Wright R, Young N, Frank M M, Lawley T J
J Invest Dermatol. 1987 Apr;88(4):388-92. doi: 10.1111/1523-1747.ep12469445.
In vivo studies have shown that human C5a, a potent complement-derived anaphylatoxin and chemoattractant, produces immediate inflammatory reactions following intradermal injection in human skin. At concentrations within its potential physiologic range, intradermal injection of C5a elicits immediate wheal and flare reactions, increased vascular permeability, mast cell degranulation, and neutrophil-rich infiltrates. To assess the relative contribution of interacting cellular elements to C5a-induced inflammation in normal human skin, purified human C5a was tested intradermally in 8 patients with bone marrow failure (BMF). Reactions to C5a in patients with BMF were compared with responses at identical test sites in healthy volunteers and other patients with cutaneous disorders. Patients with BMF demonstrated significantly less wheal and flare reactivity following intradermal injection of C5a than controls (p less than 0.05 and less than 0.02, respectively). In these studies, patients with the greatest cytopenia generally showed the least cutaneous reactivity to human C5a. Biopsies of C5a test sites in patients with BMF revealed an absence of leukocytes in marked contrast to neutrophil-rich infiltrates observed at test sites in healthy volunteers. Avidin-fluorescent and/or Giemsa staining of skin biopsies revealed no difference between the number of dermal mast cells in patients with BMF and samples of normal human skin. In addition, skin test studies with histamine (2 micrograms) and morphine (5 micrograms) performed to assess cutaneous vascular and mast cell responsiveness in patients with BMF, normal volunteers and controls with rhinitis revealed no significant differences in cutaneous reactivity to these pharmacologic agents. These in vivo studies demonstrate that patients with BMF specifically exhibit decreased cutaneous reactivity to human C5a and suggest that neutrophils make an important and an immediate contribution to inflammatory responses elicited by this anaphylatoxin.
体内研究表明，人C5a是一种强效的补体衍生过敏毒素和趋化因子，在人皮内注射后会产生即时炎症反应。在其潜在生理范围内的浓度下，皮内注射C5a会引发即时风团和潮红反应、血管通透性增加、肥大细胞脱颗粒以及富含中性粒细胞的浸润。为了评估相互作用的细胞成分对正常人皮肤中C5a诱导炎症的相对贡献，在8例骨髓衰竭（BMF）患者中进行了皮内注射纯化人C5a的试验。将BMF患者对C5a的反应与健康志愿者和其他皮肤病患者相同测试部位的反应进行比较。BMF患者皮内注射C5a后的风团和潮红反应明显低于对照组（分别为p<0.05和<0.02）。在这些研究中，血细胞减少最严重的患者通常对人C5a的皮肤反应性最低。BMF患者C5a测试部位的活检显示没有白细胞，这与健康志愿者测试部位观察到的富含中性粒细胞的浸润形成鲜明对比。皮肤活检的抗生物素蛋白荧光和/或吉姆萨染色显示，BMF患者的真皮肥大细胞数量与正常人皮肤样本之间没有差异。此外，对BMF患者、正常志愿者和鼻炎对照组进行组胺（2微克）和吗啡（5微克）的皮肤试验研究，以评估皮肤血管和肥大细胞反应性，结果显示对这些药物的皮肤反应性没有显著差异。这些体内研究表明，BMF患者对人C5a的皮肤反应性特别降低，提示中性粒细胞对这种过敏毒素引发的炎症反应做出重要且即时的贡献。
