Comparison of alveolar and interstitial macrophages in fibroblast stimulation after silica and long or short asbestos

Abstract

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.