The link between neutrophils, neutrophil extracellular traps, and NLRP3 inflammasomes: The dual effect of CD177 and its therapeutic potential in acute respiratory distress syndrome/acute lung injury

Jingying Li; Zhansheng Fang; Shumin Xu; Haiwei Rao; Junzhe Liu; Kunjian Lei; Lufei Yang; Chong Wang; Zhenguo Zeng

doi:10.17305/bb.2023.10101

Authors

Jingying Li Department of Critical Care Medicine, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China
Zhansheng Fang Department of Neurosurgery, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China; JXHC Key Laboratory of Neurological Medicine, Jiangxi, China
Shumin Xu Department of Operating Room, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China
Haiwei Rao Department of Critical Care Medicine, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China
Junzhe Liu Department of Neurosurgery, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China; JXHC Key Laboratory of Neurological Medicine, Jiangxi, China
Kunjian Lei Department of Neurosurgery, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China; JXHC Key Laboratory of Neurological Medicine, Jiangxi, China
Lufei Yang Department of Neurosurgery, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China; JXHC Key Laboratory of Neurological Medicine, Jiangxi, China
Chong Wang Department of Neurosurgery, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China; JXHC Key Laboratory of Neurological Medicine, Jiangxi, China
Zhenguo Zeng Department of Critical Care Medicine, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, China

DOI:

https://doi.org/10.17305/bb.2023.10101

Keywords:

Acute respiratory distress syndrome (ARDS), CD177, NLRP3, neutrophil extracellular traps (NETs), reactive oxygen species (ROS)

Abstract

Neutrophils are important inflammatory effector cells that protect against foreign invasion but also cause self-harm. Numerous
neutrophils infiltrate the lungs in acute respiratory distress syndrome/acute lung injury (ARDS/ALI) patients. However, the exact
impact of neutrophil infiltration on ARDS’s onset and progression remains unclear. To investigate this, we analyzed two ARDS-related
datasets from the Gene Expression Omnibus public database and discovered an association between CD177, a neutrophil-specific
surface protein, and ARDS progression. We used quantitative flow cytometry to assess CD177+ neutrophils in the peripheral blood of
clinical ARDS patients vs healthy controls, finding a significant increase in CD177+ neutrophils percentage among total neutrophils in
ARDS patients. This finding was further confirmed in ALI mouse models. Subsequent animal experiments showed that anti-CD177
effectively reduces pulmonary edema, neutrophil infiltration, and inflammatory cytokine release, along with a decrease in reactive
oxygen species (ROS) and myeloperoxidase (MPO) levels. We also established an in vitro co-culture system to mimic neutrophil and
lung epithelial cell interactions. In the anti-CD177 group, we observed decreased expression of NLRP3, caspase 1, peptidyl arginine
deiminase (PAD4), MPO, and ROS, along with a reduction in certain inflammatory cytokines. These results indicate a crucial role for the
CD177 gene in ARDS’s development and progression. Inhibiting CD177 may help mitigate excessive activation of NLRP3 inflammasomes, ROS, and neutrophil extracellular traps (NETs), thus alleviating ARDS.