Leukotriene B4 Contributes to Exhaled Breath Condensate and Sputum Neutrophil Chemotaxis in COPD

Abstract

Neutrophils have been implicated in the pathogenesis of COPD. Several chemoattractants for neutrophils have been measured in samples of exhaled breath condensate (EBC) and induced sputum (IS) from patients with COPD. The aims of this study were to compare EBC and IS supernatant neutrophil chemotactic activity (NCA) from ex-smoking subjects with COPD and healthy ex-smokers, and to assess the contribution of leukotriene B(4) (LTB(4)) to this activity. Thirty-four subjects with COPD were compared to 24 control subjects. EBC and IS chemotactic activity for neutrophils was assessed by using Boyden microchambers. The chemotactic index was used to evaluate cell migration. LTB(4) was measured by a specific enzyme immunoassay. The contribution of LTB(4) to EBC and sputum neutrophil chemotaxis was assessed by an LTB(4) receptor antagonist (U-75302; Cayman Chemical Company; Ann Arbor, MI). EBC and IS samples from both COPD patients and healthy subjects displayed significant NCA, but this activity was raised in COPD patients compared to healthy subjects. The chemotactic activity contained in sputum, however, failed to correlate with that in EBC. In COPD patients, there was a significant correlation between EBC NCA and sputum neutrophil counts. LTB(4) levels were raised in EBC samples, but not in sputum samples, from COPD subjects compared to those from healthy subjects. LTB(4) receptor antagonist concentrations (2.5 x 10(-4) mol/L) reduced by 44.6% and by 44.4%, respectively, the chemotactic activity contained in the EBC and sputum samples. EBC and IS from COPD patients have a raised NCA to which LTB(4) contributes.