促炎细胞因子
急性呼吸窘迫综合征
巨噬细胞极化
炎症
免疫学
肺泡巨噬细胞
巨噬细胞
生物
下调和上调
川地163
肺
医学
M2巨噬细胞
体外
内科学
生物化学
基因
作者
Song Chen,Haitao Li,Yang Li,Minhui Dai,Lemeng Zhang,Liu Shuai,Hongyi Tan,Pengbo Deng,Jingjing Liu,Min Zhi,Qian Li,Xiaoli Su,Long Yuan,Fengyu Lin,Yirong Zeng,Yunlong Fan,Bailing Luo,Can Hu,Pinhua Pan
标识
DOI:10.1016/j.yexcr.2019.06.031
摘要
Neutrophils activated during acute lung injury (ALI) form neutrophil extracellular traps (NETs) to capture pathogens. However, excessive NETs can cause severe inflammatory reactions. Macrophages are classified as M1 macrophages with proinflammatory effects or M2 macrophages with anti-inflammatory effects. During ALI, alveolar macrophages (AMs) polarize to the M1 phenotype. This study tested the hypothesis that NETs may aggravate ALI or acute respiratory distress syndrome (ARDS) inflammation by promoting alveolar macrophage polarization to the M1 type. Our research was carried out in three aspects: clinical research, animal experiments and in vitro experiments. We determined that NET levels in ARDS patients were positively correlated with M1-like macrophage polarization. NET formation was detected in murine ALI tissue and associated with increased M1 markers and decreased M2 markers in BALF and lung tissue. Treatment with NET inhibitors significantly inhibitor NETs generation, downregulated M1 markers and upregulated M2 markers. Regardless of LPS pre-stimulation, significant secretion of proinflammatory cytokines and upregulated M1 markers were detected from bone marrow-derived macrophages (M0 and M2) cocultured with high concentrations of NETs; conversely, M2 markers were downregulated. In conclusion, NETs promote ARDS inflammation during the acute phase by promoting macrophage polarization to the M1 phenotype. We propose that NETs play an important role in the interaction between neutrophils and macrophages during the early acute phase of ALI.
科研通智能强力驱动
Strongly Powered by AbleSci AI