Kumar R K, O'Grady R, Li W, Velan G M
School of Pathology, University of New South Wales, Sydney, Australia.
Int J Exp Pathol. 1992 Oct;73(5):573-83.
Experimental studies on particle-induced pulmonary fibrosis have not provided consistent evidence for the specific induction of fibroblast-regulating cytokines by pulmonary macrophages in response to fibrogenic as compared to non-fibrogenic particles. Using an optimized, wholly serum-free bioassay, we assessed mitogenic activity for pulmonary fibroblasts in supernatants of short-term cultures of alveolar macrophages exposed to either fibrogenic silica or non-fibrogenic titanium dioxide ducts. The responses to these supernatants were influenced by the replicative status of the target cells, in that samples which stimulated non-cycling fibroblasts caused inhibition of DNA synthesis by cycling cells when tested at the same concentration. However, both silica and titanium dioxide elicited comparable secretion of growth factor activity by macrophages, following either in-vitro or in-vivo administration of particles. In contrast, bronchoalveolar lavage fluids from animals that received intratracheal injections of silica, but not from those that received titanium dioxide, exhibited a sustained reduction in fibroblast-stimulating activity. We conclude that secretion of growth factor activity by alveolar macrophages in culture is induced by particles in a non-specific manner. However, alterations in mitogenic activity in bronchoalveolar lavage fluid may constitute a biological marker of the pattern of pulmonary injury which progresses to fibrosis.
关于颗粒诱导的肺纤维化的实验研究，尚未提供一致的证据表明，与非致纤维化颗粒相比，肺巨噬细胞在响应致纤维化颗粒时会特异性诱导成纤维细胞调节细胞因子。我们使用一种优化的、完全无血清的生物测定法，评估了暴露于致纤维化二氧化硅或非致纤维化二氧化钛导管的肺泡巨噬细胞短期培养上清液中对肺成纤维细胞的促有丝分裂活性。对这些上清液的反应受靶细胞复制状态的影响，即当以相同浓度测试时，刺激非循环成纤维细胞的样品会导致循环细胞的DNA合成受到抑制。然而，无论是在体外还是体内给予颗粒后，二氧化硅和二氧化钛都能引起巨噬细胞分泌相当的生长因子活性。相比之下，接受气管内注射二氧化硅的动物的支气管肺泡灌洗液，而不是接受二氧化钛的动物的灌洗液，其刺激成纤维细胞的活性持续降低。我们得出结论，培养中的肺泡巨噬细胞分泌生长因子活性是以非特异性方式由颗粒诱导的。然而，支气管肺泡灌洗液中有丝分裂活性的改变可能构成进展为纤维化的肺损伤模式的生物学标志物。
