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[Induction of granulomatous liver inflammation by noninfectious particles]
Abstract:
A single intravenous injection of 0.1 mg/g of zymosan led to the formation of granuloma-type clusters of mononuclears in the liver of CBA mice or (CBA X C57B1)F1 hybrid mice. The area occupied by the granulomas grows for 3 to 9 days and then gradually diminishes so that the granulomas disappear practically in one month. Hydrocortisone injected in a dose of 125 mg/kg 2 and 24 hours before or 2 and 24 hours after zymosan inhibited the initiation of granulomas but, at the same time, led to their slower involution. Mice with zymosan-induced granulomas became hypersensitive to the derivate of an endotoxin--prodigiosin, a polysaccharide obtained from S. marcescens. After intravenous infusion of a preparation of corpuscular alkaline phosphatase (CAP) granuloma-like structures also appear in the liver of rats. In distinction from zymosan-induced granulomas they persist for a much longer time (up to 27 weeks). The first signs of CAP-induced granulomas appear in 3 days. The liver per cent by volume occupied by the granulomas gradually doubles by the 15th week and then reduces. At the same time, the number of granulomas per 1 mm3 of hepatic tissue remains practically constant for 3 to 21 weeks from the moment of the induction by CAP. Their average size grows slowly and reaches maximum by the 15th week, with significant variations. Desmine and reticular fibres accumulate in the granulomas, which is evidence of active involvement of hepatic fat-accumulating cells in their formation. The results show that resident macrophages are the triggers of granulomatous inflammation of the liver.
Insights
Zymosan and corpuscular alkaline phosphatase (CAP) induce liver granulomas in mice and rats, respectively. Resident macrophages trigger this inflammation, with hydrocortisone affecting granuloma development and involution.
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Context:
- Liver granulomas are inflammatory responses to various stimuli.
- Understanding granuloma formation is crucial for treating inflammatory liver diseases.
Purpose:
- To investigate the induction and characteristics of liver granulomas using zymosan and corpuscular alkaline phosphatase (CAP).
- To explore the role of resident macrophages in zymosan-induced liver granulomas.
- To assess the effect of hydrocortisone on granuloma formation and resolution.
Summary:
- Intravenous zymosan in mice induces transient liver granulomas, while CAP in rats causes persistent granulomas.
- Hydrocortisone inhibits granuloma initiation but slows resolution; zymosan-induced granulomas increase hypersensitivity to prodigiosin.
- CAP-induced granulomas show sustained presence, with macrophage involvement and accumulation of desmin and reticular fibers, indicating hepatic fat-accumulating cell activity.
Impact:
- Identifies resident macrophages as key triggers of hepatic granulomatous inflammation.
- Provides insights into the differential kinetics and cellular involvement in zymosan- and CAP-induced liver granulomas.
- Offers potential targets for modulating inflammatory liver conditions.