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Updated: Jun 23, 2025
Visualizing Macrophage Extracellular Traps Using Confocal Microscopy
Published on: October 19, 2017
Macrophage Extracellular Traps Suppress Particulate Matter-Induced Airway Inflammation
Shenwei Gao1, Kua Zheng1, Jiafei Lou1
1Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Abstract:
Accumulating evidence has substantiated the potential of ambient particulate matter (PM) to elicit detrimental health consequences in the respiratory system, notably airway inflammation. Macrophages, a pivotal component of the innate immune system, assume a crucial function in responding to exogenous agents. However, the roles and detailed mechanisms in regulating PM-induced airway inflammation remain unclear. The current study revealed that PM had the ability to stimulate the formation of macrophage extracellular traps (METs) both in vitro and in vivo. This effect was dependent on peptidylarginine deiminase type 4 (PAD4)-mediated histone citrullination. Additionally, reactive oxygen species were involved in the formation of PM-induced METs, in parallel with PAD4. Genetic deletion of PAD4 in macrophages resulted in an up-regulation of inflammatory cytokine expression. Moreover, mice with PAD4-specific knockout in myeloid cells exhibited exacerbated PM-induced airway inflammation. Mechanistically, inhibition of METs suppressed the phagocytic ability in macrophages, leading to airway epithelial injuries and an aggravated PM-induced airway inflammation. The present study demonstrates that METs play a crucial role in promoting the phagocytosis and clearance of PM by macrophages, thereby suppressing airway inflammation. Furthermore, it suggests that activation of METs may represent a novel therapeutic strategy for PM-related airway disorders.
Insights
Particulate matter (PM) triggers airway inflammation by forming macrophage extracellular traps (METs) via PAD4. Activating METs may offer a new therapy for PM-related respiratory issues.
Area of Science:
- Immunology
- Environmental Health
- Cell Biology
Background:
- Ambient particulate matter (PM) is linked to respiratory diseases, particularly airway inflammation.
- Macrophages are key immune cells, but their role in PM-induced inflammation is not fully understood.
Purpose of the Study:
- To investigate the role and mechanisms of macrophage extracellular traps (METs) in particulate matter-induced airway inflammation.
- To explore the potential of METs as a therapeutic target for PM-related respiratory disorders.
Main Methods:
- In vitro and in vivo studies using particulate matter exposure.
- Investigated the role of peptidylarginine deiminase type 4 (PAD4) and reactive oxygen species in MET formation.
- Utilized PAD4 knockout models in macrophages and myeloid cells.
- Assessed phagocytic ability and inflammatory cytokine expression.
Main Results:
- Particulate matter stimulates the formation of macrophage extracellular traps (METs) dependent on PAD4 and reactive oxygen species.
- Genetic deletion of PAD4 in macrophages led to increased inflammatory cytokine expression.
- Mice lacking PAD4 in myeloid cells showed worsened PM-induced airway inflammation.
- Inhibiting METs impaired macrophage phagocytosis, causing airway epithelial injury and increased inflammation.
Conclusions:
- Macrophage extracellular traps (METs) are crucial for PM phagocytosis and clearance, thus suppressing airway inflammation.
- MET formation, regulated by PAD4, plays a protective role against PM-induced respiratory damage.
- Targeting MET activation presents a potential therapeutic strategy for managing particulate matter-related airway diseases.
