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Updated: Dec 9, 2025
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Novel Sca-1+ macrophages modulate the pathogenic progress of endotoxemia
Min Young Park1, Hyung Sik Kim1, Yu Sun Jeong1
1Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Abstract:
Macrophages are important innate immune cells that play crucial roles in inflammatory responses. Accumulating evidence has demonstrated macrophage heterogeneity based on biomarkers, functions, and localization. Here, we report a novel stem cell antigen-1 (Sca-1)-positive macrophage population induced in the pathological conditions caused by lipopolysaccharide (LPS). Sca-1 is only upregulated in macrophages but not in monocytes and neutrophils upon LPS injection. Sca-1+ macrophages develop from resident peritoneal macrophages. LPS-induced Sca-1+ macrophage generation was partly blocked by anti-IFN-γ antibody, suggesting a role of IFN-γ in the process. LPS-stimulated production of IL-6, TNF-α, and CCL2 is significantly lower in Sca-1+ macrophages compared to their counterpart Sca-1- macrophages. Depletion of Sca-1+ macrophages using anti-Sca-1 antibody significantly increased survival rate and reduced lung and kidney damage in an LPS-induced sepsis model. Taken together, we discovered a novel population of Sca-1+ macrophages in LPS-induced septic conditions.
Insights
Researchers discovered a new type of macrophage, stem cell antigen-1 (Sca-1)-positive macrophages, during lipopolysaccharide (LPS)-induced inflammation. These Sca-1+ macrophages are less inflammatory and their depletion improves survival in sepsis models.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages are key innate immune cells involved in inflammation.
- Macrophage heterogeneity is increasingly recognized based on markers, functions, and location.
Purpose of the Study:
- To identify and characterize novel macrophage populations in pathological conditions.
- To investigate the role of stem cell antigen-1 (Sca-1) in macrophage responses to lipopolysaccharide (LPS).
Main Methods:
- Lipopolysaccharide (LPS) injection in mice.
- Flow cytometry to detect Sca-1 expression on immune cells.
- In vivo depletion of Sca-1+ macrophages using anti-Sca-1 antibody.
- Assessment of inflammatory cytokine production (IL-6, TNF-α, CCL2).
- Evaluation of survival rates and organ damage in a sepsis model.
Main Results:
- A novel population of Sca-1-positive macrophages was identified in LPS-induced pathological conditions.
- Sca-1 upregulation was specific to macrophages, not monocytes or neutrophils, upon LPS exposure.
- LPS-induced Sca-1+ macrophage generation was partially inhibited by anti-IFN-γ antibody.
- Sca-1+ macrophages exhibited lower production of IL-6, TNF-α, and CCL2 compared to Sca-1- macrophages.
- Depletion of Sca-1+ macrophages enhanced survival and reduced organ damage in an LPS-induced sepsis model.
Conclusions:
- A novel Sca-1+ macrophage population emerges during LPS-induced septic conditions.
- These Sca-1+ macrophages may play a regulatory role in inflammation, as indicated by reduced cytokine production.
- Targeting Sca-1+ macrophages presents a potential therapeutic strategy for sepsis.
