Accession Number:

AD1166812

Title:

Neutrophil Elastase Reprograms Macrophage Function in Chronic Obstructive Pulmonary Disease

Descriptive Note:

[Technical Report, Annual Report]

Corporate Author:

VIRGINIA COMMONWEALTH UNIV CHILDREN'S HOSPITAL OF RICHMOND

Personal Author(s):

• Voynow, Judith A.

Report Date:

2021-10-01

Pagination or Media Count:

109

Abstract:

Background The relentless progression of lung disease in COPD is due in part to the failure of lung macrophage innate immune function. The failure of the macrophage to clear infections and terminate inflammation is attributed to the airway milieu in COPD but the mechanisms are not completely understood. Neutrophil elastase NE,present in the COPD airway, may subvert macrophage function from protective to pro-inflammatory. Rationale We demonstrate that NE is taken up by macrophages and targets the cytoplasm and nucleus, and NE exerts intracellular protease activity. NE degrades or modifies epigenetic regulators resulting in release of potent pro-inflammatory proteins cytokines and High Mobility Group Box 1 HMGB1, and release of macrophage extracellular traps METs. Extracellular traps are DNA strands decorated with chromatin binding proteins, myeloperoxidase and NE they trap and kill bacteria but they are also highly pro-inflammatory. Airway extracellular traps are associated with worse COPD lung disease.

Descriptors:

• health services
• medical personnel
• chemistry
• lung diseases
• cells
• proteins
• cell physiological processes
• biomedical and dental materials
• pulmonology
• polymeric films
• proteomics
• airway management
• blood
• culture media
• carrier proteins
• liquid chromatography

Subject Categories:

• Medicine and Medical Research

Distribution Statement:

[A, Approved For Public Release]