Adamson I Y, Letourneau H L, Bowden D H
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Lab Invest. 1991 Mar;64(3):339-44.
Pulmonary fibrosis in response to silica or asbestos has been attributed to secretion of fibroblast growth factors (FGF) by alveolar macrophages (AM). However, since fibrosis is interstitial, and is associated with particle retention by interstitial macrophages (IM), we have now compared the secretory activity of FGF by rat alveolar (AM) and IM in response to silica and to long or short asbestos fibers. AM were obtained by bronchoalveolar lavage, and IM by collecting macrophages that migrate from explants of a previously lavaged and perfused lung. Six weeks after instilling silica, isolated AM and IM from lungs secreted equal amounts of FGF. Six weeks after instilling short asbestos fibers in vivo, lavaged AM secreted FGF, but there was no change in fibroblast growth and no fibrosis in vivo. After long fibers, that reach the interstitium were instilled, isolated IM secreted FGF, and collagen levels were increased. When IM and AM were isolated from normal rats and exposed to the same silica or asbestos samples in vitro, it was found that all macrophage supernatants contained FGF, and the response of AM and IM was equal. The results indicate that the two macrophage populations respond equally to particles with respect to FGF secretion. The greater fibrotic reaction seen in vivo may be explained by the proximity of fibroblasts to particle-laden macrophages within the interstitium allowing more efficient transfer of FGF.
二氧化硅或石棉所致的肺纤维化被认为是肺泡巨噬细胞（AM）分泌成纤维细胞生长因子（FGF）所致。然而，由于纤维化是间质性的，且与间质巨噬细胞（IM）的颗粒潴留有关，我们现在比较了大鼠肺泡巨噬细胞（AM）和间质巨噬细胞（IM）对二氧化硅以及长或短石棉纤维的FGF分泌活性。通过支气管肺泡灌洗获得AM，通过收集从先前灌洗和灌注的肺外植体迁移的巨噬细胞获得IM。注入二氧化硅6周后，从肺中分离的AM和IM分泌等量的FGF。在体内注入短石棉纤维6周后，灌洗的AM分泌FGF，但体内成纤维细胞生长无变化且无纤维化。注入到达间质的长纤维后，分离的IM分泌FGF，且胶原蛋白水平升高。当从正常大鼠中分离出IM和AM并在体外使其暴露于相同的二氧化硅或石棉样品时，发现所有巨噬细胞上清液均含有FGF，且AM和IM的反应相同。结果表明，这两种巨噬细胞群体在FGF分泌方面对颗粒的反应相同。体内观察到的更强纤维化反应可能是由于成纤维细胞与间质内载有颗粒的巨噬细胞接近，从而使FGF的转移更有效。
