Light and electron microscopic studies on experimental nocardia-toxicosis in mice
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1Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, Japan.
Abstract:
An exotoxin (HS-6) produced by Nocardia otitidiscaviarum isolated from certain lesions of cutaneous nocardiosis of a male 82-year-old patient induced severe injuries in the pancreas, liver, stomach, small intestine, heart, thymus and kidney of male ICR mice. Mice given Nocardia-free preparation of HS-6 at a dose of 1 mg/kg of body weight developed several autophagic vacuoles in the pancreas and liver within 20 min after the i.p. injection. Thereafter, the autophagic vacuoles increased in number and size with time. About 24 hr after the administration of HS-6, the liver showed marked accumulation of fat droplets in the cytoplasm of the hepatocytes. Although they contained abundant autophagic vacuoles in the regions of RER, there were no lipomatoses in the acinar cells of the pancreas, those of the chief cells and smooth muscle cells of the stomach, Paneth cells, goblet cells, smooth muscle cells of the small intestine, and plasma cells in the digestive tract. Biochemical examinations revealed that HS-6 had no significant effect on the protein synthesis of reticulocytes. Inoculation of the Nocardia into the mouse peritoneal cavities caused marked granulomatoses in the pancreas, liver and regional lymph nodes, but did not develop autophagic vacuoles in RER regions of these organs.
Insights
The exotoxin HS-6 from Nocardia otitidiscaviarum causes severe pancreatic and liver injury in mice, characterized by rapid autophagic vacuole formation and fat accumulation. Nocardia inoculation, however, induced granulomas without autophagic vacuoles.
Area of Science:
- Microbiology
- Toxicology
- Cell Biology
Background:
- Cutaneous nocardiosis can be caused by Nocardia otitidiscaviarum.
- Exotoxins produced by bacteria can induce significant organ damage.
- Autophagy is a cellular process involved in degradation and recycling.
Purpose of the Study:
- To investigate the effects of the exotoxin HS-6 from Nocardia otitidiscaviarum on mouse organs.
- To characterize the cellular mechanisms underlying HS-6-induced toxicity.
- To differentiate the effects of the exotoxin from the effects of bacterial inoculation.
Main Methods:
- Administration of purified exotoxin HS-6 (1 mg/kg, i.p.) to male ICR mice.
- Intraperitoneal inoculation of Nocardia into mouse peritoneal cavities.
- Ultrastructural analysis of pancreas and liver tissues at various time points (20 min, 24 hr).
- Biochemical examination of reticulocyte protein synthesis.
Main Results:
- HS-6 induced rapid formation and enlargement of autophagic vacuoles in mouse pancreas and liver within 20 minutes.
- Significant accumulation of fat droplets in hepatocytes occurred 24 hours after HS-6 administration.
- No significant effect of HS-6 on reticulocyte protein synthesis was observed.
- Nocardia inoculation caused granulomatous inflammation in the pancreas, liver, and lymph nodes, but not autophagic vacuoles in RER regions.
Conclusions:
- The exotoxin HS-6 is a potent inducer of cellular injury, specifically autophagosome formation and steatosis, in mouse pancreas and liver.
- HS-6 toxicity appears to be distinct from the inflammatory response induced by Nocardia bacterial inoculation.
- Further research is warranted to elucidate the precise molecular pathways targeted by HS-6.