Pulmonary interstitial fibrosis is a devastating outcome of the chronic inflammatory response to inhaled toxins, including metals such as beryllium. Basic fibroblast growth factor (bFGF) is a potent stimulator of fibroblast, endothelial cell, and smooth muscle cell proliferation and has been linked with fibroproductive and angiogenic responses. We hypothesized that excess production of bFGF occurs in chronic beryllium disease (CBD) as well as in "idiopathic" lung disorders. Furthermore, we hypothesized that mast cells may be the source of key profibrotic growth factors in the lungs in such diseases.
To test these hypotheses, we performed immunohistochemical staining and computer-assisted morphometric analysis of lung tissue from CBD (n=13), sarcoidosis (Sar; n=10), idiopathic pulmonary fibrosis (IPF; n=11), normal control subjects (Nor; n=11), and nondiseased patients with beryllium sensitization (BeS; n=8). We observed immunore-active bFGF in [tryptase.sup.+] mast cells in both normal and diseased lung. In addition to mast cells, bFGF localized to basement membrane and endothelial cells, but not to [CD68.sup.+] macrophages. Quantitation of the volume density of (Vv) [bFGF.sup.+] cells and Vv [tryptase.sup.+] cells demonstrated a statistically significant increase in these cell populations in the lungs of patients with CBD, Sar, and IPF compared to Nor and BeS lung tissue. The highest values were observed in IPF, consistent with the severe extent of fibrotic reaction in that disorder. There was a significant correlation between Vv [bFGF.sup.+] cells and Vv [tryptase.sup.+] cells (r=0.87; p[less than]0.001). Basic [FGF.sup.+] mast cells colocalized to the periphery of granulomas (r=0.53; p[less than]0.01 for Vv granuloma) in CBD and Sar, and correlated with the Vv collagen and reticular fiber deposition as measured using pentachrome staining (r=0.78; p[less than]0.001).
We conclude that mast cells containing bFGF may contribute to the interstitial fibrotic response to environmental antigen, and may represent part of the stereotypic response to other as yet unidentified agents of granulomatous and fibrotic lung disease.
COPYRIGHT 1996 American College of Chest Physicians
COPYRIGHT 2004 Gale Group