Immunoregulation of lung fibroblast growth: alteration in asbestos-induced pulmonary fibrosis.
Initial studies on mononuclear cell-fibroblast interactions have shown that stimulated human lymphocytes produced a fibroblast growth inhibitory factor and that asbestos, a fibrogenic dust, interferes with this process in vitro. To investigate the role of these interactions in pathologies characterized by pulmonary fibrosis, we used a rat model of asbestos-induced fibrosis. Rats received a single intratracheal instillation of either saline or 10 mg of chrysotile asbestos fibres. Three months after treatment, peripheral blood mononuclear leucocytes (PBML) supernatant fractions were prepared and their effects on lung fibroblast growth measured. As for human PBML, rat PBML stimulated with Concanavalin A (Con A) produced 24 h after initiation of the cultures a soluble factor which inhibits lung fibroblast DNA synthesis and growth in a dose-dependent fashion. By contrast, Con A-stimulated PBML from rats exposed to asbestos failed to produce significant levels of fibroblast growth inhibitory activity. No significant change of total PBML number or in the proportion of circulating mononuclear cell populations was observed. Furthermore, upon stimulation with lipopolysaccharide (LPS), monocytes from asbestotic animals retained their capacity to produce interleukin (IL-1), a mediator required for lymphokine production. Our study demonstrates that suppression of FGIF production by circulating PBML occurs in animals with lung fibrosis and suggests that mechanisms other than impairment of IL-1 production may be responsible for the suppressive effect of asbestos on the production of such fibroblast regulatory lymphokine.
D000818:Animals; D001194:Asbestos / Q000494:pharmacology; D017632:Asbestos, Serpentine; D002455:Cell Division; D005347:Fibroblasts / Q000166:cytology; D006020:Glycopeptides / Q000096:biosynthesis*; D006131:Growth Inhibitors / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains
D017632:Asbestos, Serpentine; D006020:Glycopeptides; D006131:Growth Inhibitors; D007375:Interleukin-1; C020327:fibroblast proliferation inhibitor; D001194:Asbestos