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IL-15 and GM-CSF stimulated macrophages enhances phagocytic activity in ENU induced leukemic mice
Ashish Kumar Singha1, Chaitali Sarkar1, Debabrata Majumder1
1Immunology and Microbiology Lab, Dept. of Human Physiology, Tripura University, Suryamaninagar-799022, Tripura, India.
Abstract:
Murine splenic macrophage plays a decisive role in host immunity through phagocytosis against pathogens. It was reported that, macrophages also involves in phagocytosis of some tumour cells upon its activation initiated by certain cytokines produced by other immune cell or by indigenously treated. In this study, we have investigated the killing of leukemic blast cells by macrophages upon stimulated with IL-15 and GM-CSF alone or in combination in ENU challenged leukemic murine model. Along with, the release of TNF-α, IL-12 and IFN-γ by macrophages were assayed by ELISA. NO production by macrophages was also investigated. The molecular expressions like GM-CSF and TLRs were investigated for better understand of macrophage-leukemic cell interaction. Result shows that in disease condition macrophages have poor phagocytic activities which may be due to less release of TNF-α, IL-12 and IFN-γ by macrophages. This impaired phagocytic activity in leukemic mice was increase upon stimulation with IL-15 and GM-CSF.
Insights
Stimulating macrophages with IL-15 and GM-CSF enhances their phagocytic activity against leukemic cells in mice. This immune cell activation is crucial for improving host defense in leukemia models.
Area of Science:
- Immunology
- Cancer Research
- Cell Biology
Background:
- Murine splenic macrophages are vital for host immunity, exhibiting phagocytosis against pathogens and tumor cells.
- Macrophage activation, triggered by cytokines, enhances their ability to engulf tumor cells.
- Leukemic conditions can impair macrophage phagocytic functions.
Purpose of the Study:
- To investigate the effect of Interleukin-15 (IL-15) and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) on macrophage-mediated killing of leukemic blast cells.
- To assess the impact of these cytokines on the release of key immune mediators and nitric oxide (NO) production by macrophages.
- To understand the molecular mechanisms underlying macrophage-leukemic cell interactions.
Main Methods:
- Utilized an N-ethyl-N-nitrosourea (ENU) challenged leukemic murine model.
- Stimulated macrophages with IL-15 and GM-CSF, individually and in combination.
- Assayed cytokine release (TNF-α, IL-12, IFN-γ) via ELISA, measured NO production, and investigated molecular expressions (GM-CSF, TLRs).
Main Results:
- Macrophages in leukemic mice exhibited reduced phagocytic activity, correlated with lower levels of TNF-α, IL-12, and IFN-γ.
- Stimulation with IL-15 and GM-CSF significantly improved the impaired phagocytic activity of macrophages in leukemic mice.
- Cytokine stimulation and molecular expression analysis provided insights into macrophage-leukemic cell interactions.
Conclusions:
- IL-15 and GM-CSF effectively enhance macrophage phagocytosis of leukemic cells in a murine model.
- Cytokine-induced activation of macrophages represents a potential therapeutic strategy for enhancing host immunity against leukemia.
- Understanding macrophage-leukemic cell interactions is critical for developing novel immunotherapies.
