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Peritoneal macrophages exposed to purified macrophage colony-stimulating factor (M-CSF) suppress mitogen- and
Abstract:
The effect of M-CSF-exposed macrophages on murine splenic lymphocyte responses was determined. Resident peritoneal macrophages incubated with purified M-CSF for 48 hr inhibited lymphocyte proliferation to Con A, PHA, and listerial antigen as determined by [3H]TdR uptake, and inhibited Con A-stimulated lymphocyte IL 2 production. The inhibition was similar to that observed with macrophages from BCG-infected mice. Maximal suppression occurred at M-CSF concentrations of 500 U/ml or greater and when the incubation time with M-CSF was 48 hr or more. M-CSF effect was specific because rabbit anti-M-CSF IgG blocked the suppression whereas control rabbit IgG did not. Secretory products of macrophages could not be implicated in this interaction. Catalase and indomethacin, alone or together, did not reverse the inhibition. In addition, putative suppressive factors were not detected in supernatants of M-CSF-stimulated macrophages. Lymphocytes that were removed from macrophage monolayers and were recultured in medium plus Con A were able to proliferate. Macrophages stimulated by M-CSF therefore appear to have inhibitory activity for proliferating lymphocytes, and may play a role in immunoregulatory mechanisms.
Insights
Macrophage colony-stimulating factor (M-CSF) inhibits lymphocyte proliferation and IL-2 production. This M-CSF-induced macrophage activity suppresses immune responses, suggesting a role in immunoregulation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages play a critical role in immune responses.
- Macrophage colony-stimulating factor (M-CSF) is a key cytokine regulating macrophage differentiation and function.
Purpose of the Study:
- To investigate the effect of M-CSF-exposed macrophages on murine splenic lymphocyte responses.
- To determine if M-CSF influences lymphocyte proliferation and cytokine production.
Main Methods:
- Resident peritoneal macrophages were incubated with purified M-CSF.
- Lymphocyte proliferation was assessed using [3H]TdR uptake.
- Interleukin-2 (IL-2) production was measured in Concanavalin A (Con A)-stimulated lymphocytes.
Main Results:
- M-CSF-treated macrophages significantly inhibited lymphocyte proliferation to various antigens (Con A, PHA, listerial antigen).
- IL-2 production by Con A-stimulated lymphocytes was also suppressed by M-CSF-exposed macrophages.
- Maximal suppression was observed at M-CSF concentrations ≥500 U/ml and incubation times ≥48 hours.
- The inhibitory effect was specific to M-CSF, as anti-M-CSF IgG blocked suppression, while control IgG did not.
- Secretory products, catalase, and indomethacin were not implicated in the observed inhibition.
Conclusions:
- M-CSF-stimulated macrophages possess inhibitory activity towards proliferating lymphocytes.
- These findings suggest that M-CSF-mediated macrophage activity may play a role in immune regulation.