Multiple Death Pathways of Neutrophils Regulate Alveolar Macrophage Proliferation

Xiaochen Gao1,2,3,4, Weijia Zhang1,2,3,4, Nan Zhang1,2,3,4

  • 1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

Cells
|November 26, 2022
PubMed

Insights

Neutrophils in lung fluid, not bone marrow, inhibit alveolar macrophage proliferation. Targeting neutrophil death pathways may improve lung immune cell balance in respiratory diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Respiratory Medicine

Background:

  • Alveolar macrophages (AMs) are crucial for lung homeostasis, but their regulation by other immune cells, particularly neutrophils, is poorly understood.
  • Understanding neutrophil-AM interactions is vital for addressing lung inflammation and disease.

Purpose of the Study:

  • To investigate the impact of neutrophils on alveolar macrophage proliferation and function.
  • To identify mechanisms by which neutrophils influence AM homeostasis.

Main Methods:

  • Induced neutrophil migration into the lung using CXCL1.
  • Co-cultured bronchoalveolar lavage (BAL) neutrophils and bone marrow (BM) neutrophils with AMs in vitro.
  • Performed bulk RNA sequencing and analyzed publicly available data.
  • Utilized inhibitors of neutrophil death pathways.

Main Results:

  • BAL neutrophils, but not BM neutrophils, inhibited AM proliferation.
  • Neutrophils from influenza-infected mice (PR8-neutrophils) did not inhibit AM proliferation.
  • PR8-neutrophil co-culture induced IFN-α/γ and inflammatory responses in AMs.
  • BAL-neutrophil co-culture increased metabolism- and ROS-associated genes in AMs.
  • Neutrophil death pathway inhibitors abrogated BAL-neutrophil-mediated suppression of AM proliferation.

Conclusions:

  • Neutrophil cell death pathways critically regulate AM proliferation.
  • Targeting neutrophil death pathways offers a potential therapeutic strategy for enhancing AM homeostasis in respiratory diseases.

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