Terui T, Kato T, Tagami H
Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.
J Invest Dermatol. 1989 Apr;92(4):593-7. doi: 10.1111/1523-1747.ep12709634.
We provide evidence that stratum corneum (SC) activates complement through the alternative pathway to generate C5a anaphylatoxin. By immunofluorescence studies it was shown that in addition to circulating IgG autoantibody, there were anti-SC antibodies of IgM and IgA classes in the sera from normal individuals. However, all the titers were significantly lower than the level of C3 deposition between corneocytes. By contrast, no C1q deposition occurred. Immunoelectrophoretically the orthokeratotic SC homogenates were found to induce the conversion of C3 from native C3 to C3b in fresh human serum even when the classic pathway was blocked by Ca2+-chelation. Enzyme immunoassay showed that factor B split product, Bb, was generated by the SC homogenates in the Ca2+-chelated serum. Radioimmunoassay for C5a also demonstrated that the SC homogenates could generate C5a anaphylatoxin in serum to an extent similar to that in non-treated serum when restricted to the alternative pathway activation; neutrophil chemotactic activity was generated in Ca2+-chelated serum at levels comparable to that generated in non-treated fresh serum. We separated the SC samples into a cornified envelope and soluble and keratin fractions. The cornified envelope was more effective in activating complement. This activity resided in heat-stable and non-lipid substances of corneocytes. Our hypothesis is that when the SC comes in contact with serum, it activates complement mainly through the alternative pathway to induce chemotactic C5a anaphylatoxin. Hence, inflammation in normal individuals after a traumatic injury to the skin or rupture of acne comedones, or epidermal cysts and possibly the formation of subcorneal sterile pustules noted in several dermatoses are explainable through this mechanism.
我们提供证据表明，角质层（SC）通过替代途径激活补体以生成C5a过敏毒素。通过免疫荧光研究表明，除了循环IgG自身抗体外，正常个体血清中还存在IgM和IgA类抗SC抗体。然而，所有滴度均显著低于角质形成细胞之间C3沉积水平。相比之下，未发生C1q沉积。免疫电泳发现，即使经典途径被Ca2+螯合阻断，正角化SC匀浆仍能在新鲜人血清中诱导C3从天然C3转化为C3b。酶免疫测定显示，SC匀浆在Ca2+螯合血清中产生了因子B裂解产物Bb。C5a放射免疫测定也表明，当限于替代途径激活时，SC匀浆在血清中产生C5a过敏毒素的程度与未处理血清相似；在Ca2+螯合血清中产生的中性粒细胞趋化活性水平与未处理新鲜血清中产生的水平相当。我们将SC样本分离为角化包膜、可溶性和角蛋白部分。角化包膜在激活补体方面更有效。这种活性存在于角质形成细胞的热稳定和非脂质物质中。我们的假设是，当SC与血清接触时，它主要通过替代途径激活补体以诱导趋化性C5a过敏毒素。因此，正常个体在皮肤受到创伤性损伤、痤疮粉刺破裂、表皮囊肿破裂后发生的炎症，以及几种皮肤病中出现的角膜下无菌脓疱的形成，都可以通过这一机制来解释。
