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Updated: Nov 6, 2025

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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Published on: May 21, 2018

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M1 Macrophages Are More Susceptible to Necroptosis

Qin Hao1, Steven Idell1, Hua Tang1

  • 1Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

Journal of Cellular Immunology
|May 7, 2021
PubMed

Insights

M1 macrophages are more prone to necrotic cell death than M0 and M2 subtypes. This enhanced necroptosis in M1 cells relies on receptor-interacting protein kinase-3 (RIPK3) signaling, offering new insights into inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophages are key immune cells involved in host defense, inflammation, and tissue repair.
  • Macrophage polarization (M0, M1, M2) influences their function, but their role in necrotic cell death remains unclear.

Purpose of the Study:

  • To investigate the susceptibility of different macrophage subtypes to necrotic cell death.
  • To elucidate the molecular mechanisms underlying M1 macrophage necroptosis during inflammation.

Main Methods:

  • Bone marrow-derived macrophages (BMDMs) were differentiated into M0, M1, and M2 subtypes.
  • Macrophage susceptibility to necrotic cell death was assessed.
  • Key necroptosis signaling molecules, including RIPK3, were analyzed in M1 macrophages.

Main Results:

  • M1 macrophages exhibited significantly higher susceptibility to necrotic cell death compared to M0 and M2 macrophages.
  • Enhanced necroptosis in M1 macrophages was dependent on the kinase activity of receptor-interacting protein kinase-3 (RIPK3).
  • Upregulation of RIPK3, mixed lineage kinase domain-like protein (MLKL), and Z-DNA/RNA binding protein 1 (ZBP1) was observed in M1 necroptosis.

Conclusions:

  • M1 macrophages are particularly vulnerable to necroptosis, a form of programmed necrosis.
  • RIPK3 kinase activity is essential for M1 macrophage necroptosis.
  • These findings enhance our understanding of M1 macrophage roles in inflammation and tissue injury.
Keywords:
InflammationM1/M2 phenotypesMLKLMacrophage polarizationNecroptosisRIPK3ZBP1

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