Details

Autor(en) / Beteiligte

• Hansen, Michelle J
• Chan, Sheau Pyng J
• Langenbach, Shenna Y
• Dousha, Lovisa F
• Jones, Jessica E
• Yatmaz, Selcuk
• Seow, Huei Jiunn
• Vlahos, Ross
• Anderson, Gary P
• Bozinovski, Steven
• Thatcher, Thomas H.

Titel

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

Ist Teil von

• PloS one, 2014-11, Vol.9 (11), p.e113180-e113180

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2014

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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.