Piguet P F, Collart M A, Grau G E, Sappino A P, Vassalli P
Department of Pathology, University of Geneva, Switzerland.
Nature. 1990 Mar 15;344(6263):245-7. doi: 10.1038/344245a0.
The deposition of silica particles in the lung of man or experimental animals leads to silicosis, a disease of progressive respiratory failure caused by a fibrotic reaction. It has long been suspected that the phagocytosis of silica by pulmonary macrophages induces the secretion of fibrogenic factors. Several potentially fibrogenic cytokines released by macrophages have been identified, including interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF), platelet-derived growth factor, basic fibroblast growth factor and transforming growth factor-beta (TGF-beta). Here we show that TNF plays an important part in silica-induced pulmonary fibrosis in mice in that (1) a single instillation of silica leads to a marked increase in the level of lung TNF messenger RNA which lasts for greater than 70 days, while there are no obvious changes in the amounts of IL-1 alpha or TGF-beta mRNAs; and (2) silica-induced collagen deposition is almost completely prevented by anti-TNF antibody, but is significantly increased by continuous infusion of mouse recombinant TNF.
二氧化硅颗粒在人类或实验动物肺部的沉积会导致矽肺，这是一种由纤维化反应引起的进行性呼吸衰竭疾病。长期以来，人们一直怀疑肺巨噬细胞对二氧化硅的吞噬作用会诱导促纤维化因子的分泌。已经鉴定出巨噬细胞释放的几种潜在促纤维化细胞因子，包括白细胞介素-1（IL-1）、肿瘤坏死因子-α（TNF）、血小板衍生生长因子、碱性成纤维细胞生长因子和转化生长因子-β（TGF-β）。在此我们表明，TNF在小鼠二氧化硅诱导的肺纤维化中起重要作用，因为（1）单次注入二氧化硅会导致肺TNF信使RNA水平显著升高，持续超过70天，而IL-1α或TGF-β mRNA的量没有明显变化；（2）抗TNF抗体几乎完全阻止了二氧化硅诱导的胶原蛋白沉积，但通过持续输注小鼠重组TNF则显著增加。
