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The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic
Abstract:
The paralelism between the capacity of various agents to elicit chronic inflammatory responses in vivo and to induce the selective release of lysosomal enzymes from cultures of mouse peritoneal macrophages in vitro is discussed. Zymosan elicits an intense inflammatory response when injected i.m. in mice. Chrysotile asbestos produces a response of a similar nature and intensity as is seen with zymosan, while injections of acid-leached asbestos and polystyrene latex are not followed by inflammation. It is also shown that zymosan and asbestos induce a dose-dependent increase in the total enzyme activity of an inflamed muscle. On the other hand latex and acid-leached asbestos caused no significant increases in lysosomal enzyme levels. Agents eliciting inflammatory responses, such as zymosan and chrysotile asbestos induce a selective release of acid hydrolases from cultured macrophages; in contrast agents lacking the capacity to induce inflammation, such as latex and acid-leached chrysotile asbestos, do not induce the release of lysosomal enzymes from cultured macrophages.
Insights
Agents that cause inflammation, like zymosan and chrysotile asbestos, trigger lysosomal enzyme release from macrophages. Non-inflammatory agents, such as latex and acid-leached asbestos, do not. This highlights a key mechanism in chronic inflammation.
Area of Science:
- Immunology
- Cell Biology
- Toxicology
Background:
- Chronic inflammation involves complex cellular responses.
- Lysosomal enzymes play a role in inflammatory processes.
- Understanding agent-specific macrophage activation is crucial.
Purpose of the Study:
- To investigate the relationship between an agent's ability to cause inflammation in vivo and its effect on macrophage lysosomal enzyme release in vitro.
- To compare the inflammatory potential of zymosan, chrysotile asbestos, acid-leached asbestos, and polystyrene latex.
Main Methods:
- In vivo studies: Injection of agents into mouse muscles to assess inflammatory response.
- In vitro studies: Incubation of mouse peritoneal macrophages with agents to measure lysosomal enzyme release.
- Biochemical assays to quantify total enzyme activity in inflamed muscle tissue.
Main Results:
- Zymosan and chrysotile asbestos induced significant inflammation and dose-dependent increases in muscle lysosomal enzyme activity.
- Acid-leached asbestos and polystyrene latex did not elicit inflammatory responses or increase enzyme levels.
- Inflammatory agents (zymosan, asbestos) selectively released acid hydrolases from macrophages, while non-inflammatory agents (latex, leached asbestos) did not.
Conclusions:
- A direct correlation exists between an agent's capacity to induce inflammation in vivo and its ability to stimulate lysosomal enzyme release from macrophages in vitro.
- Lysosomal enzyme release from macrophages is a key cellular event in the pathogenesis of inflammation induced by specific agents.
- This study provides insights into the mechanisms underlying agent-induced chronic inflammation.