concanavalin-a and Asbestosis

In order to study changes in lung histology and lymphocyte function during the development of pneumoconiosis, three groups of Balb/c mice were intratracheally instilled with either saline, chrysotile asbestos or silica particles and then sacrificed at different times. Asbestos-instilled mice showed collagen deposits at 2 months while silica-instilled mice showed severe fibrosis at that time. Stimulation of splenic cells with LPS was not affected by instillation of the toxic particles. Stimulation with PHA and ConA, however, induced increased responses especially at 3 and 6 months after instillation of asbestos or silica. A diminution of mitogen-induced proliferation was observed in aged mice. There was no correlation between changes in splenic cell proliferation and development of fibrosis. Asbestos fibers added in vitro, inhibited PHA and ConA-induced proliferation, partially due to prostaglandin (PG) production and to the presence of the fibers during the assay. When asbestos fibers were removed by washing, no inhibition was observed. Moreover, actual stimulation of proliferation was noted when PG production was inhibited in vitro with indomethacin. In contrast, in vivo treatment of asbestos-instilled mice with indomethacin had no effect on the development of lung pathology.

Topics: Animals; Asbestosis; Cell Adhesion; Concanavalin A; Indicators and Reagents; Lipopolysaccharides; Lung; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Phytohemagglutinins; Pulmonary Fibrosis; Silicosis; Spleen

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)

Topics: Animals; Asbestosis; Biological Products; Cells, Cultured; Concanavalin A; Cytokines; Fibroblast Growth Factors; Fibroblasts; Glycopeptides; Lung; Lymphocytes; Macrophages; Male; Pulmonary Fibrosis; Rats; Rats, Inbred Strains; Therapeutic Irrigation