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Bidirectional modulation of TNF‐a production by alveolar macrophages in asbestos‐induced pulmonary fibrosis
Author(s) -
Ouellet Sophie,
Yang Huixin,
Aubin Rmy A.,
Hawley Robert G.,
Wenckebach Georg F. C.,
Lemaire Irma
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.53.3.279
Subject(s) - biology , pulmonary fibrosis , asbestos , immunology , tumor necrosis factor alpha , fibrosis , alveolar macrophage , macrophage , microbiology and biotechnology , pathology , medicine , in vitro , materials science , biochemistry , metallurgy
Bronchoalveolar lavage (BAL) cells were isolated from rats 1, 3, and 6 weeks after a single intratracheal instillation of saline, UICC chrysotile asbestos (5 mg), or silica (5 mg). In asbestos‐exposed rats, the pulmonary response was characterized by a significant increase in the number of alveolar macrophages (AMs) and the appearance of fibrotic lesions within 1 week. By contrast, mixed macrophage and neutrophile accumulations were observed in the silica group without evidence of fibrosis. Tumor necrosis factor‐ot (TNF‐αoduction by lipopolysaccharide (LPS)‐stimulated BAL cells from asbestos‐treated rats was significantly lower than controls 1 and 3 weeks after exposure. However, by 6 weeks higher levels of TNF‐a production were noticeable in this group. Decreases in LPS‐induced TNF‐αon were also observed with BAL cells from silica‐treated animals at all time points studied. Lower levels of TNF‐a were not related to decreased BAL cell viability or the presence of a significant proportion of neutrophils in the silica group. Furthermore, biphasic changes in TNF‐αtion seen in the asbestos group were correlated with concomitant decreases (3 weeks) and increases (6 weeks) in levels of TNF‐α mRNA in AMs. These data indicate that lower levels of TNF‐α resulted from inhibition at the gene expression level and provide evidence for bidirectional modulation of TNF‐α production by AMs during inflammatory reactions.