期刊
BIOMOLECULES
卷 11, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/biom11081065
关键词
neutrophil elastase; cystic fibrosis; chronic obstructive pulmonary disease; bronchiectasis; bronchopulmonary dysplasia; antiprotease; glycosaminoglycan
资金
- Cystic Fibrosis Foundation [VOYNOW19G0]
- Department of Defense Peer Reviewed Medical Research Program (PRMRP) Investigator-Initiated Research Award [PR180925]
- NIH [R01 HL146811-01A1]
- CDMRP [1102709, PR180925] Funding Source: Federal RePORTER
NE plays a role in chronic inflammatory airway diseases and can affect the airway environment, inducing airway remodeling and disrupting epithelial repair.
Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic obstructive pulmonary disease, non-CF bronchiectasis, and bronchopulmonary dysplasia. Although NE facilitates leukocyte transmigration to the site of infection and is required for clearance of Gram-negative bacteria, it also activates inflammation when released into the airway milieu in chronic inflammatory airway diseases. NE exposure induces airway remodeling with increased mucin expression and secretion and impaired ciliary motility. NE interrupts epithelial repair by promoting cellular apoptosis and senescence and it activates inflammation directly by increasing cytokine expression and release, and indirectly by triggering extracellular trap release and exosome release, which magnify protease activity and inflammation in the airway. NE inhibits innate immune function by digesting opsonins and opsonin receptors, degrading innate immune proteins such as lactoferrin, and inhibiting macrophage phagocytosis. Importantly, NE-directed therapies have not yet been effective in preventing the pathologic sequelae of NE exposure, but new therapies are being developed that offer both direct antiprotease activity and multifunctional anti-inflammatory properties.
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