Kreuger M R, Tames D R, Mariano M
Department of Pathology, School of Veterinary Medicine, University of São Paulo, SP, Brazil.
Immunology. 1998 Oct;95(2):278-82. doi: 10.1046/j.1365-2567.1998.00542.x.
The microbicidal activity of macrophages in an inflammatory milieu has been related to the production of a large number of cytokins and intermediary metabolites of oxygen and nitrogen among them, nitric oxide (NO). Considering that granulomatous inflammation is predominantly composed of macrophages and epithelioid cells, we decided to investigate the participation of NO in this peculiar type of inflammation. Two models were used: glass cover slip implantation into the subcutaneous tissue of mice and, the inoculation of live bacillus Calmette-Guérin (BCG) into the footpad of the animals. Using a histochemical method for the detection of NO synthase and of the concentration of citrulin metabolized by cells obtained from cover slips implanted on different time intervals or BCG-activated peritoneal cells, it was possible to demonstrate that epithelioid cells do not produce NO. Cells from granuloma induced by BCG inoculation express NO synthase, with different degrees of reactivity with a higher intensity in the cytoplasm of cells located in the edge of the lesions. The expression of NO synthase in the cytoplasm of these cells decreases with the age of the lesions. It could also be demonstrated that in mice treated with l-name, an inhibitor of NO metabolism, the lesions induced by BCG lost the granulomatous architecture, were necrotic, and had a significant increase in the bacillary load of the lesion. These data allow us to conclude that NO production by macrophages is a determining factor in the organization of the granulomatous lesion and that it also controls the bacterial load in BCG-induced lesions in mice.
巨噬细胞在炎症环境中的杀菌活性与大量细胞因子以及氧和氮的中间代谢产物（其中包括一氧化氮（NO））的产生有关。鉴于肉芽肿性炎症主要由巨噬细胞和上皮样细胞组成，我们决定研究NO在这种特殊类型炎症中的作用。我们使用了两种模型：将玻璃盖玻片植入小鼠皮下组织，以及将活卡介苗（BCG）接种到动物脚垫中。通过组织化学方法检测NO合酶以及从在不同时间间隔植入的盖玻片或BCG激活的腹膜细胞中获得的细胞代谢的瓜氨酸浓度，结果表明上皮样细胞不产生NO。接种BCG诱导的肉芽肿细胞表达NO合酶，其反应程度不同，位于病变边缘的细胞胞质中的反应强度更高。这些细胞胞质中NO合酶的表达随病变年龄的增长而降低。还可以证明，在用L-精氨酸甲酯（L-name，一种NO代谢抑制剂）处理的小鼠中，BCG诱导的病变失去了肉芽肿结构，出现坏死，并且病变中的细菌载量显著增加。这些数据使我们得出结论，巨噬细胞产生的NO是肉芽肿病变形成的决定性因素，并且它还控制小鼠BCG诱导病变中的细菌载量。
