Role of complement and polymorphonuclear cells in demethylchlortetracycline-induced phototoxicity in guinea pigs. Inhibition by decomplementation in vivo.
Role of complement and polymorphonuclear cells in demethylchlortetracycline-induced phototoxicity in guinea pigs. Inhibition by decomplementation in vivo.
复制标题
补体和多形核细胞在去甲基金霉素诱导的豚鼠光毒性中的作用。
DOI：
10.1172/jci111088
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Gigli,I
中科院分区：
文献类型：
--
作者：
Lim,HW;Novotny,H;Gigli,I
本研究以去甲基金霉素作为外源性光毒物质的原型。在体外，含去甲基金霉素的血清暴露于紫外线-A辐射后，总补体溶血活性和C4、C2、C3、C5活性降低。此外，还产生了对人多形核细胞的趋化活性，这种趋化活性与人C5具有耐热性和抗原性，但与人C3无关。在体豚鼠皮内注射去甲基金霉素溶液，然后进行紫外线A照射，可诱发光毒性损伤。在0-3+的范围内，动物在20h时的最大反应为2.5。这种临床反应与真皮细胞的渗透有关，在24 h时，中性粒细胞占29+/-2%。用环磷酰胺治疗中性粒细胞减少的豚鼠，评估中性粒细胞的参与。在这些豚鼠中，去甲基金霉素和紫外线-A诱导的最大反应为0.75+/-0.5，组织学上与真皮中1.2+/-0.5%的中性粒细胞有关。在先天性C4缺乏的豚鼠和经眼镜蛇毒素治疗后失补的豚鼠中，研究了补体在这一过程中的作用。与正常豚鼠相比，C4缺乏的豚鼠在6h出现最大反应0.83+/-0.16，并在24 h内消退，眼镜蛇毒素处理的豚鼠在0.5h和6h出现最大反应0.5，这些临床变化与血管通透性增加有关，这一结果被静脉注射伊文思蓝溶液的豚鼠所证实。在补体系统正常的动物中，光毒性损伤部位有强烈的局部性蓝化。相比之下，在去补位的豚鼠中只观察到了轻微的蓝色。这些数据表明，正常数量的多形核细胞和完整的补体系统是去甲基金霉素诱导的光毒性损伤充分发展所必需的。
In this study, demethylchlortetracycline was used as a prototype of exogenous phototoxic substances. In vitro, exposure of serum containing demethylchlortetracycline to ultraviolet-A irradiation resulted in the diminution of total complement hemolytic activity and C4, C2, C3, and C5 activities. In addition, chemotactic activity for human polymorphonuclear cells was generated, which was thermostable and antigenically related to human C5 but not human C3. In vivo, phototoxic lesions were induced in guinea pigs upon intradermal injections of demethylchlortetracycline solution, followed by ultraviolet-A irradiation. On a scale of 0-3+, the animals developed a maximal response of 2.5 at 20 h. This clinical response was associated with cellular infiltrate in the dermis, consisting of 29 +/- 2% of neutrophils at 24 h. The participation of the polymorphonuclear cells was evaluated in guinea pigs rendered neutropenic by treatment with cyclophosphamide. In these guinea pigs, demethylchlortetracycline and ultraviolet-A induced a maximal response of 0.75 +/- 0.5, which was associated histologically with 1.2 +/- 0.5% neutrophils in the dermis. The role of complement in this process was studied in guinea pigs congenitally deficient in C4, and in guinea pigs decomplemented by treatment with cobra venom factor. In contrast to normal guinea pigs, C4-deficient animals exhibited a maximal reaction of 0.83 +/- 0.16 at 6 h, which subsided within 24 h. Cobra venom factor-treated guinea pigs developed a maximal response of 0.5 at 0.5 and at 6 h. These clinical changes were associated with the development of an increased vascular permeability, as demonstrated by studies using guinea pigs injected intravenously with Evans blue solution. In animals with a normal complement system, there was intense localized bluing at the sites of phototoxic lesion. In contrast, only minimal bluing was observed in decomplemented guinea pigs. These data indicate that a normal number of polymorphonuclear cells and an intact complement system are required for the full development of demethylchlortetracycline-induced phototoxic lesions.Images