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Basic Fibroblast Growth Factor and Its Receptors in Idiopathic Pulmonary Fibrosis and Lymphangioleiomyomatosis

Division of Environmental and Occupational Health Sciences and Pulmonary Division, Department of Medicine, National Jewish Medical and Research Center; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine and Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; Department of Diffuse Lung Diseases and Respiratory Failure, Clinical Research Center, National Kinki-Chuo Hospital for Chest Diseases, Osaka, Japan; and Department of Medicine, San Francisco General Hospital, San Francisco, California

Correspondence and requests for reprints should be addressed to Yoshikazu Inoue, M.D., Ph.D., Department of Diffuse Lung Diseases and Respiratory Failure, Clinical Research Center, National Kinki-Chuo Hospital for Chest Diseases, 1180 Nagasone-cho, Sakai, Osaka 591-8555, Japan. E-mail: giichi{at}kch.hosp.go.jp

Basic fibroblast growth factor (bFGF) is a potent mitogenic factor for smooth muscle cells, myofibroblasts, and fibroblasts, proliferation of which is a hallmark of idiopathic pulmonary fibrosis (IPF) and lymphangioleiomyomatosis (LAM). Mast cells produce bFGF and have been associated with pulmonary fibrosis. We hypothesize that smooth muscle cell/myofibroblast–like cells will be spatially associated with bFGF-containing mast cells and that bFGF receptors will be expressed on the effector cells in IPF and LAM. We performed quantitative immunohistochemistry for bFGF, mast cell tryptase, smooth muscle actin for smooth muscle cell/myofibroblast–like cells, and fibroblast growth factor receptors (Flg, Bek) and measured collagen and elastic fiber in lung sections from IPF (n = 14), LAM (n = 9), and control lung (n = 10). IPF and LAM lung contained more smooth muscle cell/myofibroblast–like cells than did control lung. bFGF-containing mast cells were abundant both in IPF and LAM and were associated with collagen, elastic fibers, and smooth muscle cell/myofibroblast–like cells in IPF. Flg was expressed on epithelial cells, endothelial cells, smooth muscle cell/myofibroblast–like cells, and macrophages in IPF. In LAM, Flg was expressed on epithelial cells adjacent to smooth muscle cell/myofibroblast–like cell aggregates. Bek was expressed dominantly on smooth muscle cell/myofibroblast–like cells in LAM and on smooth muscle cell/myofibroblast–like cells as well as neutrophils in IPF. These data suggest that mast cell–derived bFGF might exert fibrogenic, proliferative effects on smooth muscle cell/myofibroblast–like cells through its receptors.

Key Words: mast cells • extracellular matrix • myofibroblasts • fibroblast growth factor receptors • lung

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