Bone marrow derived M2 macrophages protected against lipopolysaccharide-induced acute lung injury through inhibiting oxidative stress and inflammation by modulating neutrophils and T lymphocytes responses

Abstract

Acute lung injury (ALI) is characterized by aggravated inflammatory responses and the subsequent alveolar-capillary injury for which there are no specific therapies available currently. The present study was designed to investigate the protective roles of bone marrow derived M₂ macrophages (M₂ BMDMs) in lipopolysaccharide (LPS) induced ALI. M₂ BMDMs were obtained from bone marrow cells stimulated with M-CSF and IL-4. Mice received M₂ BMDMs intratracheally 3 h after LPS administration. Histology and wet/dry (W/D) weight ratio, activated immune cells and total protein were detected. Cytokines production were measured in vivo and vitro study. The effects of PD-L1 blockade on M₂ BMDMs were calculated. The results showed that M₂ BMDMs administration reduced the infiltration of neutrophils, inhibited the oxidative stress, while increased the counts of CD3⁺T lymphocytes as well as CD4⁺CD25⁺ regulatory T lymphocytes. Further, M₂ BMDMs suppressed the TNF-α, IL-1β and IL-6 production, while increased the IL-10 production. Blockade of PD-L1/PD-1 pathway reversed cytokines production of M₂ BMDMs in the BALF. These findings indicated that M₂ BMDMs might be a promising therapeutic strategy for LPS-induced ALI through inhibiting oxidative stress and inflammation by modulating neutrophils and T lymphocytes responses.

Keywords: Acute lung injury; Bone marrow derived M(2) macrophage; Neutrophil; PD-L1; Regulatory T lymphocyte.