Human mast cell basic fibroblast growth factor in pulmonary fibrotic disorders.
Mast cells (MCs) are abundant in fibrotic tissue, although their role in fibrogenesis remains obscure. Recent studies suggest MCs may produce basic fibroblast growth factor (bFGF). To evaluate the hypothesis that MC bFGF contributes to the fibrotic response in human interstitial lung disease, we studied lung tissue, bronchoalveolar lavage fluid and serum in 1) idiopathic pulmonary fibrosis, 2) chronic beryllium disease and sarcoidosis, 3) control subjects with no disease or who were beryllium sensitized with normal lung histology. Diseased subjects underwent clinical assessments to stage disease severity. We determined that most bFGF+ cells in lung interstitium are MCs and are most abundant in idiopathic pulmonary fibrosis. Distribution of bFGF+ MCs matched that of extracellular matrix deposition and correlated with the extent of fibrosis morphometrically. Only one bFGF isoform (17.8 kd) was found in idiopathic pulmonary fibrosis and chronic beryllium disease lung tissues and interacted with heparin-like molecules in the lung. Using a human MC line, we verified that MCs express bFGF mRNA and protein that localizes to cytoplasmic granules. Clinically, bFGF concentrations in bronchoalveolar lavage fluid and serum were highest in disease states and correlated with bronchoalveolar lavage cellularity and severity of gas exchange abnormalities, supporting a role for MC bFGF in the pulmonary fibrotic response and its clinical consequence.
Inoue
Y
Y
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
King
T E
TE
Tinkle
S S
SS
Dockstader
K
K
Newman
L S
LS
D000328:Adult; D000368:Aged; D001607:Berylliosis / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002460:Cell Line; D003094:Collagen / Q000235:genetics / Q000276:immunology; D004547:Elastic Tissue / Q000276:immunology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D012507:Sarcoidosis / Q000378:metabolism
D016222:Fibroblast Growth Factor 2; D003094:Collagen