Fibroblast mitogens in bronchoalveolar lavage (BAL) fluid from asbestos-exposed subjects with and without clinical evidence of asbestosis: no evidence for the role of PDGF, TNF-alpha, IGF-1, or IL-1 beta.
Asbestosis is a fibrotic lung disease resulting from inhalation of asbestos fibres. Its pathogenesis is poorly understood but probably involves stimulation of fibroblast proliferation and collagen production by mediators released from inflammatory and resident lung cells. In vitro studies have implicate PDGF, TNF-alpha, IGF-1, TGF-beta, and IL-1 in asbestosis, but the role of these mediators in vivo is not known. This study aimed to characterize mediators in bronchoalveolar lavage (BAL) fluid from patients exposed to asbestos with (n = 24) or without (n = 34) asbestosis, compared with ten normal subjects. Human lung fibroblasts were exposed to serial dilutions of BAL fluids and the effects on fibroblast proliferation were assessed. The median mitogenic activity of BAL fluid from asbestos-exposed (17 per cent above medium control, range 3-44 per cent) and asbestosis (14 per cent, range 2-60 per cent) groups was higher than that of BAL fluid from controls (10 per cent, range 2-20 per cent; P < 0.01 and P < 0.05, respectively), but there was no significant difference between the patient groups. The mitogenic activity of BAL fluids was not reduced by incubation with neutralizing antibodies to PDGF-AA, PDGF-AB, PDGF-BB, TNF-alpha, IGF-1, and IL-1 beta. We conclude that BAL fluids from patients exposed to asbestos contain mitogens for human lung fibroblasts, but that PDGF, TNF-alpha, IGF-1, or IL-1 beta do not contribute to this activity.
Mutsaers
S E
SE
Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, University College London Medical School, Rayne Institute, U.K. s.mutsaers@ucl.ac.uk
Harrison
N K
NK
McAnulty
R J
RJ
Liao
J Y
JY
Laurent
G J
GJ
Musk
A W
AW
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D017638:Asbestos, Crocidolite / Q000009:adverse effects; D001195:Asbestosis / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000502:physiology; D007375:Interleukin-1 / Q000276:immunology / Q000502:physiology; D008875:Middle Aged; D008906:Mining; D016273:Occupational Exposure; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology
D000906:Antibodies; D018836:Inflammation Mediators; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D017638:Asbestos, Crocidolite; D007334:Insulin-Like Growth Factor I