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2024

Clin Immunol. 2024 Jun:263:110206. doi: 10.1016/j.clim.2024.110206. Epub 2024 Apr 8.

P75^NTR+CD64+ neutrophils promote sepsis-induced acute lung injury

Di Fu, Shan Gao, Jia-Nan Li, Yan-Hui Cui, Yan-Wei Luo, Yan-Jun Zhong, Qiao Li, Cong Luo, Ru-Ping Dai, Ru-Yi Luo, Zhao-Lan Hu

Department of Anesthesiology, The Xiangya Hospital, Central South University, Changsha City, Hunan 410008, China. Anesthesia Medical Research Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha City, Hunan 410011, China. Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha City, Hunan 410011, China. Department of Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Service type: Knockout mice

Abstract

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75^NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75^NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75^NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75^NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75^NTR activity by soluble p75^NTR extracellular domain peptide (p75^ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75^NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Keywords: CD64(+) neutrophils; Phagocytosis; Sepsis-induced acute lung injury; p75(NTR).

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