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Related Experiment Video

Updated: Oct 12, 2025

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
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Inflammasome-Dependent Peroxiredoxin 2 Secretion Induces the Classical Complement Pathway Activation.

Cheol Ho Park1,2, Hyun Sook Lee1,3, Man Sup Kwak1,4

  • 1Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, Korea.

Immune Network
|November 19, 2021
PubMed
Summary

Inflammasome activation triggers the secretion of peroxiredoxins (Prxs) via gasdermin-D. Secreted Prx2 then activates the classical complement pathway by binding to C1q.

Keywords:
Classical complement pathwayGasdermin DInflammasomePeroxiredoxin 2

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Area of Science:

  • Cellular Biology
  • Immunology
  • Biochemistry

Background:

  • Peroxiredoxins (Prxs) are key antioxidant enzymes involved in cellular defense.
  • Prxs can be released extracellularly, acting as damage-associated molecular patterns, but their secretion mechanism is unclear.
  • The role of Prxs in immune system activation, particularly complement pathways, requires further investigation.

Purpose of the Study:

  • To investigate if inflammasome activation serves as a secretory mechanism for Prxs.
  • To identify the specific Prxs secreted upon inflammasome activation.
  • To determine the effect of secreted Prxs on the classical complement pathway.

Main Methods:

  • Utilized J774A.1 murine macrophage cell line to study inflammasome activation and Prx secretion.
  • Employed HEK293T cells for transfection-based analysis of Prx secretion pathways.
  • Confirmed Prx binding to C1q and assessed their impact on classical complement activation.

Main Results:

  • NLRP3 inflammasome activation induced secretion of Prx1, Prx2, Prx5, and Prx6 in a caspase-1 dependent manner.
  • Gasdermin-D (GSDMD) mediated the secretion of Prx1 and Prx2.
  • Secreted Prx1 and Prx2 bind to C1q, with Prx2 uniquely activating the classical complement pathway.

Conclusions:

  • Inflammasome activation is a novel secretory pathway for Prxs, mediated by GSDMD.
  • Secreted Prx2 plays a role in initiating the classical complement cascade through C1q interaction.
  • These findings link Prx secretion to innate immune responses and complement system activation.