Host-Defense Function of Anuclear Polymorphonuclear Neutrophil in Lung Injury

Polymorphonuclear neutrophils (PMN) function through rapid mobilization to the site of infection and are primary effectors of the innate immune response. Activated PMN extrude genomic DNA to form web-like structures called Neutrophil Extracellular Traps (NETs). After NET release (NETosis), the PMN generates anuclear cells (PMNcyto). We found that 50% of PMN in lung microvessels had transitioned to PMN cytoplasts (PMNcyto) within 24h exposure to endotoxemia. Despite being anuclear, PMNcyto displayed characteristics distinct from PMN. They showed rapid velocity compared to PMN and the ability to migrate across the endothelial barrier, phagocytosis of bacteria, and bactericidal activity. Adoptive transfer of PMNcyto into Pseudomonas aeruginosa (PA) infected mice showed a markedly reduced inflammatory lung injury. Unlike PMN, the host defense function of PMNcyto waned over time, first observed by in vivo imaging loss in velocity. Upon further investigation using seahorse assay, we observed a loss in mitochondrial functions. Mitochondrial transplantation restored the host defense and anti-inflammatory function of PMNcyto. An increase in ATP production, enhanced bactericidal efficiency, and prevented lung tissue injury were observed upon mitochondrial transplantation. These results identify a pivotal role of PMNcyto generation following PMN NETosis as a fundamental host defense mechanism and restoration of tissue homeostasis.

Author dc:creator

• Nithish Raj Prasad (23292055)

• Engineering, Biomedical
• Health Sciences, Pharmacology

Statement dc:rights

• In Copyright
• Open Access after 2028-01-01

DOI dc:identifier

https://doi.org/10.25417/uic.31451749.v1

OAI identifier oai:identifier

oai:figshare.com:article/31451749