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Release of a cytotoxic factor by macrophages stimulated with adjuvant-active peptidoglycans
Abstract:
Bacterial peptidoglycans (PG) possess various immunomodulating activities, including the ability to inhibit the growth of some experimental tumors. We report here that PG induce the release by mouse (DBA/2 and C3H/HeJ) peritoneal macrophages of a cytotoxic factor (CF) that is active on L-929 cells and a 3-methylcholanthrene-induced tumor cell line but inactive on normal fibroblasts. Only the adjuvant-active PG (extracted from Bacillus megaterium and Staphylococcus aureus) were good inducers of the CF, whereas the adjuvant inactive PG (extracted from Micrococcus lysodeikticus and Corynebacterium poinsettiae) exhibited only weak activity. The CF was released within 2 hours of contact with PG either in serum-free or serum-containing media. The CF was inhibited neither by serum nor by the protease inhibitors that have been tested. It was stable for 30 minutes at 56 degrees C but inactivated after being heated for 10 minutes at 80 degrees C. After gel filtration, a single peak of activity at 80-90 kilodaltons was found. Chromatofocusing showed that the isoelectric point of the CF was 4.8.
Insights
Bacterial peptidoglycans (PG) induce macrophages to release a cytotoxic factor (CF) that selectively kills tumor cells. This immune response is linked to the adjuvant activity of specific PG, highlighting their therapeutic potential.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Bacterial peptidoglycans (PG) exhibit immunomodulatory properties, including anti-tumor effects.
- Macrophages are key immune cells involved in recognizing bacterial components.
Purpose of the Study:
- To investigate the ability of bacterial peptidoglycans (PG) to induce the release of a cytotoxic factor (CF) from macrophages.
- To characterize the properties and specificity of the PG-induced CF.
Main Methods:
- Incubation of mouse peritoneal macrophages with various bacterial peptidoglycans (PG).
- Assay of cytotoxic factor (CF) activity against tumor cell lines and normal fibroblasts.
- Characterization of CF stability, molecular weight, and isoelectric point.
Main Results:
- Adjuvant-active PG (from Bacillus megaterium and Staphylococcus aureus) effectively induced CF release.
- The CF demonstrated selective cytotoxicity towards tumor cells, sparing normal fibroblasts.
- The CF was heat-stable up to 56°C, had a molecular weight of 80-90 kDa, and an isoelectric point of 4.8.
Conclusions:
- Bacterial peptidoglycans (PG) stimulate macrophages to produce a tumor-selective cytotoxic factor (CF).
- The induction of CF is dependent on the adjuvant activity of the PG.
- The characterized CF shows potential as an anti-cancer agent.