Inflammatory alveolar macrophage-derived microvesicles damage lung epithelial cells and induce lung injury

Lanyu Zhang1, Jie Gao1, Chunni Qin1

  • 1Department of Cardiopulmonary Bypass, State key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Immunology Letters
|November 6, 2021
PubMed

Insights

Inflammatory microvesicles from alveolar macrophages worsen acute lung injury by reducing epithelial sodium channels. Targeting these microvesicles may offer a new treatment for acute respiratory distress syndrome.

Area of Science:

  • Pulmonary Medicine
  • Cell Biology
  • Immunology

Background:

  • Microvesicles (MVs) in bronchoalveolar lavage fluid (BALF) are implicated in acute lung injury/acute respiratory distress syndrome (ALI/ARDS).
  • The specific role of alveolar macrophage (AM)-derived MVs in ALI/ARDS pathogenesis and their impact on lung epithelial cells remain unclear.

Purpose of the Study:

  • To investigate the effects of AM-derived MVs on lung epithelial cells and their in vivo contribution to ALI/ARDS.
  • To explore the potential of targeting AM-derived MVs as a therapeutic strategy for ALI/ARDS.

Main Methods:

  • MVs were isolated from mouse BALF and mouse alveolar macrophage (MHS) cells using sequential centrifugation.
  • In vitro studies involved delivering MVs to lung epithelial cells.
  • In vivo studies utilized intratracheal delivery of MVs to mice.
  • Enzyme-linked immunosorbent assay (ELISA) and Western blotting were employed to assess protein expression (TNF-α, α-ENaC, γ-ENaC, Na+,K+-ATPase).

Main Results:

  • BALF-derived MVs (BALF-MVs) and AM-derived MVs (AM-MVs) were rich in tumor necrosis factor-α (TNF-α).
  • Inflammatory BALF-MVs and AM-MVs reduced the expression of epithelial sodium channel subunits (α-ENaC, γ-ENaC) and Na+,K+-ATPase in lung epithelial cells.
  • Antibodies against TNF-α neutralized the effects of inflammatory AM-MVs in vitro.
  • In vivo, inflammatory AM-MVs induced lung tissue damage, increased injury scores, impaired alveolar fluid clearance, and downregulated key ion transport proteins in lung tissues.

Conclusions:

  • Inflammatory AM-derived MVs contribute to lung injury and pulmonary edema in ALI/ARDS.
  • These MVs exert their effects, at least partly, through TNF-α.
  • AM-derived MVs represent a potential novel therapeutic target for ALI/ARDS.