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Updated: Mar 27, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Sepsis induces incomplete M2 phenotype polarization in peritoneal exudate cells in mice
Nobuo Watanabe1, Yusuke Suzuki1, Sadaki Inokuchi1
1Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1193 Japan.
Background:
Macrophages can differentiate into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes upon exposure to a pathogen or a cytokine microenvironment. However, M1/M2 macrophage polarization in polymicrobial sepsis has not been fully characterized.
Methods:
The polarity of peritoneal exudate (PE) cells from mice that had undergone cecal ligation and puncture (CLP) and the response of those cells to lipopolysaccharide (LPS) in terms of cytokine and chemokine expression were examined.
Results:
PE cells from CLP mice demonstrated a shift toward the M2 phenotype in terms of marker enzyme expression. In addition, the CLP-derived PE cells showed apparent unresponsiveness to LPS stimulation with regard to expression of pro-inflammatory cytokines such as TNF-α, while the expression of anti-inflammatory cytokines such as IL-10 was induced. Nevertheless, the CLP-PE cells failed to express M2 chemokines including chemokine (C-C motif) ligand 17 (CCL17), CCL22, and CCL24, all of which are important for T cell recruitment.
Conclusions:
The results suggested that a shift of naïve monocytes/macrophages to the M2 phenotype, along with the lack of M2 chemokine expression in septic monocytes/macrophages, might be responsible for immunosuppression after sepsis.
Insights
Sepsis shifts macrophages to an anti-inflammatory M2 state, but these cells fail to express key M2 chemokines, potentially causing immune suppression after infection.
Area of Science:
- Immunology
- Cell Biology
- Sepsis Research
Background:
- Macrophages exhibit plasticity, polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes.
- The M1/M2 macrophage polarization dynamics in polymicrobial sepsis remain incompletely understood.
Purpose of the Study:
- To characterize macrophage polarization in polymicrobial sepsis.
- To investigate the functional response of septic macrophages to lipopolysaccharide (LPS) stimulation.
Main Methods:
- Cecal ligation and puncture (CLP) model in mice to induce polymicrobial sepsis.
- Analysis of peritoneal exudate (PE) cells for M1/M2 phenotype markers.
- Assessment of cytokine and chemokine expression in response to LPS.
Main Results:
- PE cells from CLP mice exhibited a shift towards the M2 phenotype, indicated by marker enzyme expression.
- Septic PE cells showed suppressed pro-inflammatory cytokine (e.g., TNF-α) production upon LPS stimulation.
- Anti-inflammatory cytokine (e.g., IL-10) expression was induced in septic PE cells.
- Crucially, septic PE cells failed to express M2 chemokines (CCL17, CCL22, CCL24) essential for T cell recruitment.
Conclusions:
- Polymicrobial sepsis induces a shift in monocytes/macrophages towards the M2 phenotype.
- The absence of M2 chemokine expression in septic macrophages may contribute to post-septic immunosuppression.
- These findings highlight a potential mechanism for immune dysregulation during sepsis recovery.
