ABSTRACT
Our studies indicate the effects of in vivo asbestos exposure on the ability of alveolar macrophages (AM) to elaborate a chemoattractant for fibroblast using a rat model of asbestos inhalation. Two groups of rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over a total period of 4 weeks) to either amphibole (crocidolite) or serpentine (chrysotile) asbestos. A group of control rats were sham-exposed to clean air only. The animals were sacrificed 2-5 months after the cessation of exposure. The AM were obtained from the 3 exposure groups in 2 different rat strains by the bronchoalveolar lavage and the cultured in RPMI-1640 medium for 24-96 hr at 37 degrees C. The supernatants from cultured AM were tested for chemotactic activity towards fetal rat skin fibroblasts in a chemotactic assay using 8 microns pore-size filters. The culture supernatants of AM obtained from crocidolite-exposed rats exhibited a significantly greater chemotactic activity towards rat fibroblasts than similar culture supernatants from sham-exposed control animals (p < 0.01) in both rat strains. Significant chemotactic activity was observed after chrysotile exposure (p < 0.05) in ACI rats but not in Fischer-344 rats. Maximal chemoattractant release from AM was noted after 48 hr in culture. Preliminary characterization of the chemoattractant has shown that it is a thermolabile and trypsin sensitive factor whose activity was partially reduced after dialysis. Since AM accumulate at sites of intrapulmonary asbestos deposition, these findings may have relevance to the pathologic accumulation of interstitial lung fibroblasts which occurs during asbestos-mediated lung injury.
Subject(s)
Asbestos/toxicity , Chemotactic Factors/metabolism , Macrophages, Alveolar/physiology , Skin Physiological Phenomena , Administration, Inhalation , Animals , Asbestos/administration & dosage , Asbestos, Crocidolite , Asbestos, Serpentine , Bronchoalveolar Lavage Fluid , Cells, Cultured , Fibroblasts/physiology , Macrophages, Alveolar/drug effects , Rats , Rats, Inbred ACI , Rats, Inbred F344 , Reference ValuesABSTRACT
We have studied the effects of in vivo asbestos exposure on the surface immune-associated (Ia) antigen expression and distribution of alveolar macrophage subpopulations defined by continuous iso-osmotic Percoll gradients (density range: 1.006 to 1.123 g/ml) using a rat model of asbestos inhalation. Two groups of rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 4 weeks) to either amphibole (crocidolite) or serpentine (chrysotile) asbestos. A group of control rats was sham-exposed to clean air only. Alveolar macrophages from rats of three groups were obtained by bronchoalveolar lavage. During exposure, distinct differences appeared within 7 days of asbestos exposure, and some of these findings persisted in the crocidolite-exposed group for as long as 2 to 5 months after the cessation of exposure. Furthermore, relatively greater proportions of Ia-antigen positive cells were detected in several density fractions obtained from both asbestos-exposed groups (especially the crocidolite-exposed group). Multinucleated alveolar macrophages were seen frequently in all Percoll fractions after both types of asbestos inhalation. A significant proportion of multinucleated alveolar macrophages in these fractions expressed surface Ia-antigen positivity. The finding of enriched numbers of higher-density phagocytes in bronchoalveolar lavage cell subpopulations from asbestos-exposed rats may reflect the presence of newly recruited-immature monocytes and/or macrophages at sites of intrapulmonary asbestos deposition. Also, increased proportions of Ia-antigen positive cells suggest that a part of them were functionally activated.
Subject(s)
Asbestos/pharmacology , Asbestosis/immunology , Histocompatibility Antigens Class II/biosynthesis , Macrophages, Alveolar/immunology , Administration, Inhalation , Animals , Asbestos, Crocidolite , Asbestos, Serpentine , Asbestosis/pathology , Centrifugation, Density Gradient , Disease Models, Animal , Histocompatibility Antigens Class II/drug effects , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/pathology , Male , Rats , Rats, Inbred F344Subject(s)
Asbestos/pharmacology , Histocompatibility Antigens Class II/immunology , Macrophages/immunology , Administration, Intranasal , Animals , Asbestos/administration & dosage , Asbestos, Crocidolite , Asbestos, Serpentine , Asbestosis/immunology , Female , Macrophages/drug effects , Male , Phagocytosis/drug effects , Pulmonary Alveoli/cytology , Rats , Rats, Inbred ACI , Rats, Inbred F344ABSTRACT
Asbestos inhalation can cause pulmonary fibrosis and is associated with a variety of immunological abnormalities. The purpose of this study was to evaluate the effects of asbestos inhalation on interleukin-1 (IL-1) and interleukin-2 (IL-2) production in a rodent model. Two groups of rats were exposed, by intermittent inhalation, to either amphibole (crocidolite) or serpentine (chrysotile) asbestos. A third (control) group of rats was sham exposed to clean air. Animals from the three exposure groups were thereafter immunized (or not immunized) with fetal calf serum antigens. In order to assay interleukin activity, supernatants were generated from cultures containing alveolar macrophages and autologous splenic lymphocytes, and from cultures containing alveolar macrophages alone. Using assay systems designed to detect IL-1 and IL-2 functional activity, the supernatants were evaluated for their capacity to stimulate lymphoproliferation and fibroblast DNA synthesis. Macrophage-lymphocyte co-culture supernatants, when obtained from immunized, asbestos exposed rats, contained greater IL-1 and IL-2 activity than identical supernatants from immunized, sham exposed animals. These between group differences were not, however, observed in supernatants from unimmunized rats, or when supernatants were generated in the absence of immune lymphocytes. These observations suggest that asbestos exposure is associated with enhanced activation of lymphocytes by antigens. The possible relevance of these findings to asbestos related fibrogenesis and immunological stimulation is discussed.