Acute respiratory distress syndrome (ARDS) is a common respiratory critical syndrome with no effective therapeutic intervention. Neutrophils function in the overwhelming inflammatory process of acute lung injury (ALI) caused by ARDS; however, the phenotypic heterogeneity of pulmonary neutrophils in ALI/ARDS remains largely unknown. Here, using single-cell RNA sequencing, we identify two transcriptionally and functionally heterogeneous neutrophil populations (Fth1 hi Neu and Prok2 hi Neu) with distinct locations in LPS-induced ALI mouse lungs. Exposure to LPS promotes the Fth1 hi Neu subtype, with more inflammatory factors, stronger antioxidant, and decreased apoptosis under the regulation of interleukin-10. Furthermore, prolonged retention of Fth1 hi Neu within lung tissue aggravates inflammatory injury throughout the development of ALI/ARDS. Notably, ARDS patients have high ratios of Fth1 to Prok2 expression in pulmonary neutrophils, suggesting that the Fth1 hi Neu population may promote the pathological development and provide a marker of poor outcome.
Keyphrases
- acute respiratory distress syndrome
- lps induced
- oxidative stress
- single cell
- extracorporeal membrane oxygenation
- inflammatory response
- mechanical ventilation
- lipopolysaccharide induced
- pulmonary hypertension
- end stage renal disease
- rna seq
- randomized controlled trial
- ejection fraction
- chronic kidney disease
- high throughput
- anti inflammatory
- poor prognosis
- newly diagnosed
- prognostic factors
- intensive care unit
- binding protein
- patient reported