concanavalin-a and Pulmonary-Fibrosis

The role of lymphocytes in bleomycin (Bleo)-induced lung injury remains obscure. In normal hamsters, peribronchial lymphatic tissue (PBLT) has been found to contain a large population of T lymphocytes responsive to interleukin 2 (IL-2) but not to IL-4. Lung injury induced by a single intratracheal instillation of Bleo in hamsters has been ameliorated by cyclosporin A (CyA). In the present study, using this model, PBLT-derived lymphocyte function was explored for 28 days after Bleo instillation. Increase in PBLT lymphocytes occurred at five time points investigated, reaching highest values on day +7 (p < 0.0025). Cell proliferation in response to concanavalin A was enhanced, while IL-2 +/- the mitogen had no effect. In contrast to its inactivity in the normal hamster, in the Bleo-injured animal IL-4 alone induced T cell proliferation (p = 0.0077) on day +7. CyA therapy initially suppressed and delayed recovery of the number of lymphocytes and their activation. The results of this study suggest the existence of a vulnerable period in Bleo-induced lung injury and indicate that lymphocytes participate in the pathogenesis of the insult to the tissue. The unresponsiveness to IL-2 and the emergence of cellular response to IL-4 indicate immune deviation in PBLT-derived T cells.

Topics: Animals; Anti-Bacterial Agents; Bleomycin; Bronchi; Concanavalin A; Cricetinae; Cyclosporine; Immunosuppressive Agents; Interleukin-2; Interleukin-4; Lymphatic System; Lymphocyte Activation; Male; Mesocricetus; Pulmonary Fibrosis; Spleen; T-Lymphocytes

Previous studies have not clearly defined the role of cell-mediated immunity in bleomycin-induced lung injury. In this report the functional activity of T lymphocytes obtained from minced lung preparations, bronchoalveolar lavage, and blood of rabbits treated with bleomycin was examined in cell proliferation and cell-mediated cytotoxicity assays. Four days after instillation of bleomycin (10 units/kg) into the right lung, histologic examination revealed mononuclear cell interstitial infiltrates and alveolar exudates. Right lung bronchoalveolar lavage (BAL) cell counts were similar in both groups, but the percentage of lymphocytes and neutrophils was elevated in bleomycin-treated groups (25% vs. 7% and 35% vs. 0% respectively; p less than 0.05). Spontaneous proliferation of cultured BAL and blood lymphocytes was similar in bleomycin-treated rabbits and controls. After 24 h of incubation with interleukin-2 (IL-2), BAL lymphocytes from bleomycin-treated rabbits had nearly a 4-fold greater proliferative response than lymphocytes from untreated rabbits. Concanavalin-A-dependent cell-mediated cytotoxicity (CDCMC) assays were performed to evaluate cytolytic lymphocyte activity. Spontaneous CDCMC activity was not detected in BAL fluid or in blood lymphocytes from either treated or control animals. After 24 h of incubation with IL-2, significant CDCMC activity was detected in lung lymphocytes from bleomycin-treated animals, but not in lung lymphocytes from control animals. These results indicate that stimulated lymphocytes are present in the lungs of rabbits 4 days after exposure to bleomycin.

Topics: Animals; Bleomycin; Bronchoalveolar Lavage Fluid; Concanavalin A; Disease Models, Animal; Immunity, Cellular; Interleukin-2; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Pulmonary Fibrosis; Rabbits

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

Lung macrophages may play an important role in the pathogenesis of pulmonary sarcoidosis. In this study, the ability of pulmonary macrophages and blood monocytes from sarcoidosis patients, normal controls and disease controls to provide the accessory signal necessary for the concanavalin A-induced activation of normal blood T cells was examined. Blood monocytes from all groups supplied a significantly greater accessory signal than lung macrophages. The accessory capacity of lavage macrophages from sarcoidosis patients varied over a wide range and correlations were sought between these values and other parameters of disease activity. Whilst there was no correlation with clinical parameters, accessory function of alveolar macrophages correlated significantly with the percentage of T helper cells in bronchoalveolar lavage (BAL) fluid (p less than 0.05) and, more closely, with the T helper:T suppressor ratio in BAL fluid (p less than 0.01). This interrelationship between macrophage activity and the T cell infiltrate favours the probability that both cell types participate in the sarcoid disease process and raises the possibility that T cells of both helper and suppressor phenotypes contribute to the pathogenesis.

Topics: Adult; Aged; Antigen-Presenting Cells; Bronchoalveolar Lavage Fluid; Concanavalin A; Female; Humans; Lung Diseases; Lymphocyte Activation; Macrophages; Male; Middle Aged; Monocytes; Pulmonary Alveoli; Pulmonary Fibrosis; Sarcoidosis; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

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

Topics: Alveolitis, Extrinsic Allergic; Body Fluids; Bronchi; Concanavalin A; Cytotoxicity, Immunologic; Humans; Lymphocyte Activation; Pulmonary Alveoli; Pulmonary Fibrosis; Sarcoidosis; Therapeutic Irrigation

Mitogenic preparations of nonviable lysed cells and purified membranes of Mycoplasma pulmonis induced interstitial pneumonia and tracheitis after intranasal administration to pathogen-free rats. The pneumonia, characterized by peribronchial, perivascular, and alveolar wall infiltration by lymphocytes, was indistinguishable from that produced by viable M. pulmonis. Both pathologic and mitogenic effects were significanlty reduced by prior treatment of membranes with heat or proteolytic enzyme. Intranasal administration of the thymus-derived-cell mitogen, concanavalin A, produced interstitial pneumonia but not tracheitis. These results indicate a correlation of mitogenicity and pathogenicity and suggest that activation of thymus-derived lymphocytes is the major cause of the pneumonia resulting from infections with M. pulmonis.

Topics: Animals; Cell Membrane; Concanavalin A; Female; Germ-Free Life; Hot Temperature; Lymphocyte Activation; Male; Mycoplasma pneumoniae; Peptide Hydrolases; Pulmonary Fibrosis; Rats; Rats, Inbred Strains; Tracheitis

An animal model of environmental lung disease is described in which phytomitogen, antigen, or both, are administered in aerosol form to previously immunized or immunologically naive rabbits. Inhalation of concanavalin A alone induced an interstitial pneumonitis in nonimmunized rabbits. Inhalation of concanavalin A alone induced an interstitial pneumonitis in nonimmunized rabbits. Inhalation of bovine serum albumin (BSA) alone typically produced only focal eosinophilic granulomas in BSA-immunized animals, and no injury whatever in nonimmune animals. However, simultaneous administration of BSA-concanavalin A aerosol mixtures to BSA-immunized rabbits induced a severe interstitial pneumonitis and granulomatous vasculitis, together with areas of frank parenchymal necrosis. When repeated on a chronic basis over a 4- or 8-week interval, challenge with BSA-concanavalin A aerosols resulted in both acute necrotic lesions as well as areas of frank interstitial fibrosis. Necrotic foci in acutely injured lungs were associated with interstitial deposits of BSA, rabbit anti-BSA antibody, and complement. Electron microscopy revealed numerous neutrophils within the pulmonary interstitial spaces of these animals, often in association with collagen and elastin fibers. The pattern of injury in immune rabbits induced by antigen-concanavalin A aerosols, in its nonnecrotizing form, is consistent with that of an extrinsic allergic alveolitis. However, the severe, necrotizing form of acute injury closely resembles changes seen in Wegener's granulomatosis. Possible mechanisms of injury produced by antigen and phytomitogen inhalation are discussed.

Topics: Aerosols; Alveolitis, Extrinsic Allergic; Animals; Concanavalin A; Drug Interactions; Lung; Male; Pulmonary Fibrosis; Rabbits; Serum Albumin, Bovine

Topics: Aerosols; Animals; Antigen-Antibody Reactions; Concanavalin A; Disease Models, Animal; Female; Immunity; Immunity, Cellular; Pulmonary Fibrosis; Rabbits; Respiratory Hypersensitivity; Serum Albumin, Bovine; T-Lymphocytes