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IL-17A and serum amyloid A are elevated in a cigarette smoke cessation model associated with the persistence of pigmented macrophages, neutrophils and activated NK cells
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 11, p e113180 (2014)
- Publication Year :
- 2014
-
Abstract
- While global success in cessation advocacy has seen smoking rates fall in many developed countries, persistent lung inflammation in ex-smokers is an increasingly important clinical problem whose mechanistic basis remains poorly understood. In this study, candidate effector mechanisms were assessed in mice exposed to cigarette smoke (CS) for 4 months following cessation from long term CS exposure. BALF neutrophils, CD4+ and CD8+ T cells and lung innate NK cells remained significantly elevated following smoking cessation. Analysis of neutrophil mobilization markers showed a transition from acute mediators (MIP-2α, KC and G-CSF) to sustained drivers of neutrophil and macrophage recruitment and activation (IL-17A and Serum Amyoid A (SAA)). Follicle-like lymphoid aggregates formed with CS exposure and persisted with cessation, where they were in close anatomical proximity to pigmented macrophages, whose number actually increased 3-fold following CS cessation. This was associated with the elastolytic protease, MMP-12 (macrophage metallo-elastase) which remained significantly elevated post-cessation. Both GM-CSF and CSF-1 were significantly increased in the CS cessation group relative to the control group. In conclusion, we show that smoking cessation mediates a transition to accumulation of pigmented macrophages, which may contribute to the expanded macrophage population observed in COPD. These macrophages together with IL-17A, SAA and innate NK cells are identified here as candidate persistence determinants and, we suggest, may represent specific targets for therapies directed towards the amelioration of chronic airway inflammation.
- Subjects :
- Male
Pulmonology
Neutrophils
lcsh:Medicine
Mice
0302 clinical medicine
Interleukin 23
Medicine and Health Sciences
Macrophage
lcsh:Science
Immune Response
0303 health sciences
Mice, Inbred BALB C
Multidisciplinary
biology
Interleukin-17
Flow Cytometry
3. Good health
Killer Cells, Natural
Interleukin 10
Granulocyte macrophage colony-stimulating factor
Models, Animal
medicine.symptom
Bronchoalveolar Lavage Fluid
medicine.drug
Research Article
Chronic Obstructive Pulmonary Disease
Immunology
Inflammation
Real-Time Polymerase Chain Reaction
Macrophage elastase
03 medical and health sciences
Matrix Metalloproteinase 12
Macrophages, Alveolar
medicine
Animals
Serum amyloid A
Interleukin 6
030304 developmental biology
Serum Amyloid A Protein
business.industry
lcsh:R
Biology and Life Sciences
030228 respiratory system
biology.protein
lcsh:Q
Smoking Cessation
Tobacco Smoke Pollution
business
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....7f1269654e51ec5c970ce42ce291dba1