title: Smoking status and anti-inflammatory macrophages in bronchoalveolar lavage and induced sputum in COPD.
abstract: BACKGROUND
  Macrophages have been implicated in the pathogenesis of COPD. M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties. We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD. Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD.
  
  
  METHODS
  114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months). BAL was collected from 71 patients. CD163+ macrophages were quantified in BAL and sputum cytospins. Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants.
  
  
  RESULTS
  Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 × 10(4)/ml, p = 0.001 respectively). The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001). BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003). No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum.
  
  
  CONCLUSIONS
  Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters.
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands. L.I.Z.Kunz@lumc.nl
authors.forename: Lisette I Z
authors.initials: LI
authors.lastname: Kunz
authors.forename: Thérèse S
authors.initials: TS
authors.lastname: Lapperre
authors.forename: Jiska B
authors.initials: JB
authors.lastname: Snoeck-Stroband
authors.forename: Simona E
authors.initials: SE
authors.lastname: Budulac
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Simone
authors.initials: S
authors.lastname: van Wijngaarden
authors.forename: Jasmijn A
authors.initials: JA
authors.lastname: Schrumpf
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D016014:Linear Models; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000032:analysis; D012907:Smoking / Q000009:adverse effects / Q000276:immunology*; D016540:Smoking Cessation; D000074606:Smoking Prevention; D013183:Sputum / Q000166:cytology / Q000276:immunology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D011956:Receptors, Cell Surface