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Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 2026-2034

Mast Cell Basic Fibroblast Growth Factor in Silicosis

HIRONOBU HAMADA, VAL VALLYATHAN, CARLYNE D. COOL, ELIZABETH BARKER, YOSHIKAZU INOUE, and LEE S. NEWMAN

Division of Environmental and Occupational Health Sciences and Pulmonary Division and Department of Medicine, National Jewish Medical and Research Center, and Division of Pulmonary Science and Critical Care Medicine and Departments of Pathology, Medicine, and Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; National Institute for Occupational Safety and Health, Morgantown, West Virginia; and National Kinki-Chuo Hospital for Chest Diseases, Osaka, Japan

To investigate the role of mast cells (MC) and their fibrogenic growth factors in silicosis, we performed quantitative immunohistochemistry for MC tryptase and for basic fibroblast growth factor (bFGF) in lung tissue from silicotic and control subjects. Anti-bFGF antibody was bound to lung MC, basement membrane, endothelial cells, and smooth-muscle cells. Morphometric analysis revealed that the volume density (Vv) of MC was increased in silicotic lung and that the Vv of bFGF-positive (bFGF+) cells was significantly higher than normal in silicotic lung. Most MC contained bFGF (rho  = 0.88, p < 0.001). The Vv of collagen/reticulin fibers was increased in silicosis and correlated with the Vv of bFGF+ cells (rho  = 0.81, p < 0.001). Immature silicotic nodules contained bFGF+ MC throughout the loose array of collagen/reticulin fibers. In large, mature nodules, the density of collagen/reticulin fibers was higher, and bFGF+ MC were found only in the nodule periphery. Because of this circumferential MC alignment in silicotic nodules, we observed a negative correlation between the Vv of bFGF+ MC and the density of collagen/reticulin fibers in silicotic nodules (rho  = -0.80, p < 0.001) and between the Vv of all other nodule-associated cells and the density of collagen/reticulin fibers in the hypocellular nodule centers (rho  = -0.84, p < 0.001). We conclude that MC that produce bFGF may play an important role in the development of silicosis.




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