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Asbestos-activated peritoneal macrophages release a factor(s) which inhibits lymphocyte mitogenesis
Abstract:
Intraperitoneal asbestos injection in mice has previously been reported to elicit an activated macrophage population. In the present study supernatants from such macrophages were tested for their effect on thymocyte mitogenesis in response to concanavalin A; control supernatants were obtained from saline- and latex-elicited macrophages. Supernatants from asbestos-elicited macrophages were significantly inhibitory to thymocyte mitogenesis while saline- and latex-elicited macrophages did not release significant amounts of such activity. Asbestos-activated macrophage supernatants were inhibitory in a dose-dependent way and the activity was not secreted by macrophages from mice which had received asbestos in the long term. The inhibitory activity was partially dialysable. Supernatants prepared by treating macrophages in vitro with a lethal dose of asbestos were not inhibitory suggesting that the inhibitory activity in the supernatants of asbestos-activated macrophages did not leak from dead or dying cells. The asbestos macrophage supernatant was also significantly inhibitory to mature T-cell-enriched spleen cells but had no effect on fibroblasts, suggesting that the inhibitory effect could be lymphoid cell specific.
Insights
Supernatants from asbestos-activated macrophages inhibit thymocyte proliferation. This inhibitory effect, observed with short-term asbestos exposure, suggests a specific immune response to asbestos fibers.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- Intraperitoneal asbestos injection in mice is known to activate macrophages.
- Activated macrophages can release various factors influencing immune responses.
- The specific effects of asbestos-elicited macrophage supernatants on lymphocyte proliferation were previously uncharacterized.
Purpose of the Study:
- To investigate the effect of supernatants from asbestos-activated macrophages on thymocyte mitogenesis.
- To compare the activity of asbestos-elicited macrophage supernatants with those from saline- and latex-elicited macrophages.
- To determine the specificity and characteristics of the inhibitory activity.
Main Methods:
- Collection of supernatants from macrophages elicited by intraperitoneal injection of asbestos, saline, or latex in mice.
- Testing the effect of these supernatants on concanavalin A-induced thymocyte proliferation.
- Assessing dose-dependency, duration of exposure effects, dialyzability, and specificity against fibroblasts and mature T-cells.
Main Results:
- Supernatants from asbestos-elicited macrophages significantly inhibited thymocyte mitogenesis.
- This inhibitory activity was dose-dependent and not observed with long-term asbestos exposure.
- The activity was partially dialyzable, not due to dead cells, and specifically inhibited lymphoid cells but not fibroblasts.
Conclusions:
- Asbestos-activated macrophages release soluble factors that inhibit T-cell proliferation.
- The inhibitory activity appears to be specific to lymphoid cells and is transient, linked to acute asbestos exposure.
- These findings suggest a complex immunomodulatory role of macrophages in response to asbestos exposure.