Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis.
A complex series of interactions between immunocompetent cells and fibroblasts exists. Because pulmonary fibrosis may result from an increased number of collagen-producing fibroblasts, we studied the production of fibroblast growth factors derived from alveolar macrophages (AM) and peripheral blood mononuclear leukocytes (PBML) during the development of asbestos-induced fibrosis. Three groups of rats received, respectively, a single intratracheal injection of saline (control), 5 mg of asbestos, and 10 mg of asbestos. Bronchoalveolar lavage (BAL) and PBML isolation were performed on each animal 1, 3, and 6 months after instillation. Differential cell analyses revealed no significant change in the BAL cell populations except for a small but significant increase in the proportion of lymphocytes in the 10-mg group at 1 month and in both asbestos groups at 3 months. Similar analyses of PBML revealed only a small reduction in total PBML in the 10-mg group at 6 months. Bronchoalveolar cells (98% AM) from control rats spontaneously released a fibroblast growth factor (FGF), whereas Con-A-stimulated PBML of the same animals produced fibroblast growth inhibitory activity (FGIF). One month after asbestos exposure, when fibrotic lesions were apparent, AM production of FGF was significantly enhanced, and such increase persisted for as long as 6 months. By contrast, no significant change in FGIF production by Con-A-stimulated PBML was seen at the 1-month interval. However, 3 months after exposure, there was a significant suppression of FGIF production by PBML from rats in the 10-mg group and at 6 months by PBML from rats in both asbestos groups.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001195:Asbestosis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D001688:Biological Products / Q000502:physiology*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006020:Glycopeptides / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D007507:Therapeutic Irrigation
D001688:Biological Products; D016207:Cytokines; D006020:Glycopeptides; C020327:fibroblast proliferation inhibitor; D003208:Concanavalin A; D005346:Fibroblast Growth Factors