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Disruption of transient receptor potential melastatin 2 decreases elastase release and bacterial clearance in

XiaoWei Qian1,2, Hang Zhao3, XinZhong Chen1

  • 11 Department of Anesthesiology, Women's Hospital, School of Medicine, Zhejiang University, China.

Innate Immunity
|March 3, 2018
PubMed

Insights

Transient Receptor Potential Melastatin 2 (TRPM2) channels are crucial for neutrophil bacterial clearance. TRPM2 facilitates calcium (Ca2+) influx, enhancing elastase release and survival against Gram-negative bacteria like E. coli.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Neutrophils are key immune cells for eliminating Gram-negative bacteria.
  • Elastase release by neutrophils is essential for bacterial clearance.
  • Calcium (Ca2+) influx is critical for neutrophil elastase release and bacterial killing.

Purpose of the Study:

  • To investigate the role of the calcium-permeable cation channel TRPM2 in neutrophil-mediated bacterial clearance.
  • To elucidate the mechanism by which TRPM2 influences elastase release and survival during bacterial infection.

Main Methods:

  • Utilized TRPM2 knockout (TRPM2-KO) and wild-type (WT) mice neutrophils.
  • Exposed neutrophils to Escherichia coli and stimulated with fMLP.
  • Assessed bacterial burden, elastase release, p38 MAPK phosphorylation, and intracellular Ca2+ levels.

Main Results:

  • TRPM2-KO neutrophils exhibited increased bacterial burden and reduced elastase release after E. coli exposure.
  • Septic TRPM2-KO mice showed decreased survival rates.
  • fMLP-stimulated TRPM2-KO neutrophils had lower elastase release, reduced p38 MAPK phosphorylation, and diminished intracellular Ca2+ concentration compared to WT neutrophils.

Conclusions:

  • TRPM2 plays a significant role in bacterial clearance by neutrophils.
  • TRPM2-mediated Ca2+ influx regulates elastase release, partly through p38 MAPK phosphorylation.
  • TRPM2 is a potential therapeutic target for enhancing neutrophil antibacterial functions.
Keywords:
Transient receptor potential melastatin 2bacterial clearanceelastaseneutrophilssepsis

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