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

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 recept...

Full description

Saved in:
Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2024-06, Vol.263, p.110206
Main Authors: Fu, Di, Gao, Shan, Li, Jia-Nan, Cui, Yan-Hui, Luo, Yan-Wei, Zhong, Yan-Jun, Li, Qiao, Luo, Cong, Dai, Ru-Ping, Luo, Ru-Yi, Hu, Zhao-Lan
Format: Article
Language:English
Subjects:
Acute Lung Injury - etiology
Acute Lung Injury - immunology
Animals
Cytokines - immunology
Cytokines - metabolism
Female
Humans
Lipopolysaccharides
Lung - immunology
Lung - pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins
Neutrophils - immunology
Neutrophils - metabolism
NF-kappa B - immunology
NF-kappa B - metabolism
Phagocytosis - immunology
Receptors, IgG - genetics
Receptors, IgG - immunology
Receptors, IgG - metabolism
Receptors, Nerve Growth Factor - genetics
Receptors, Nerve Growth Factor - immunology
Receptors, Nerve Growth Factor - metabolism
Sepsis - complications
Sepsis - immunology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 ) in peripheral blood of mice and patients with sepsis-induced ALI. p75 CD64 neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75 gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64 neutrophils. In vitro, p75 CD64 neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75 activity by soluble p75 extracellular domain peptide (p75 -Fc) boosted CD64 neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75 CD64 neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.
ISSN:1521-7035