STUDY OBJECTIVES: Neutrophilic inflammation is a major feature of COPD. Several factors in bronchial secretions have been identified as chemoattractants for neutrophils. The present study was designed to assess the contribution of interleukin (IL)-8 and leukotriene B(4) (LTB(4)) to neutrophil chemotaxis evoked by sputum obtained from patients with established COPD. DESIGN: Sputum supernatant of 20 patients with COPD was used as chemoattractant in a 96-well chemotaxis chamber, with subsequent quantification of migrated cells by a luminescence assay. The contribution of IL-8 and LTB(4) to chemotaxis was determined by addition of a neutralizing antibody and a selective receptor antagonist, respectively. MEASUREMENTS AND RESULTS: COPD sputum caused neutrophil chemotaxis in a concentration-dependent manner, with a maximum response evoked with a 10-fold dilution of the original sample. Pretreatment of sputum or neutrophils with either an anti-IL-8 antibody or the LTB(4) antagonist, SB 201146, led to a concentration-dependent inhibition of sputum-induced neutrophil chemotaxis, with a maximum suppression (mean +/- SEM) of 29.2 +/- 4.9% (p < 0.001) from baseline by 100 ng/mL of anti-IL-8 antibody, and 45.6 +/- 7% (p < 0.02) by 10 micro mol/L of SB 201146. The combination of the anti-IL-8 antibody and SB 201146 inhibited neutrophil chemotaxis, but this was not significantly greater than the effect of SB 201146 or anti-IL-8 alone. CONCLUSIONS: These data confirm the importance of IL-8 and LTB(4) as chemoattractants for neutrophils in bronchial secretions from patients with COPD, and suggest that specific inhibitors may have therapeutic potential in COPD.
STUDY OBJECTIVES:Neutrophilic inflammation is a major feature of COPD. Several factors in bronchial secretions have been identified as chemoattractants for neutrophils. The present study was designed to assess the contribution of interleukin (IL)-8 and leukotriene B(4) (LTB(4)) to neutrophil chemotaxis evoked by sputum obtained from patients with established COPD. DESIGN: Sputum supernatant of 20 patients with COPD was used as chemoattractant in a 96-well chemotaxis chamber, with subsequent quantification of migrated cells by a luminescence assay. The contribution of IL-8 and LTB(4) to chemotaxis was determined by addition of a neutralizing antibody and a selective receptor antagonist, respectively. MEASUREMENTS AND RESULTS:COPD sputum caused neutrophil chemotaxis in a concentration-dependent manner, with a maximum response evoked with a 10-fold dilution of the original sample. Pretreatment of sputum or neutrophils with either an anti-IL-8 antibody or the LTB(4) antagonist, SB 201146, led to a concentration-dependent inhibition of sputum-induced neutrophil chemotaxis, with a maximum suppression (mean +/- SEM) of 29.2 +/- 4.9% (p < 0.001) from baseline by 100 ng/mL of anti-IL-8 antibody, and 45.6 +/- 7% (p < 0.02) by 10 micro mol/L of SB 201146. The combination of the anti-IL-8 antibody and SB 201146 inhibited neutrophil chemotaxis, but this was not significantly greater than the effect of SB 201146 or anti-IL-8 alone. CONCLUSIONS: These data confirm the importance of IL-8 and LTB(4) as chemoattractants for neutrophils in bronchial secretions from patients with COPD, and suggest that specific inhibitors may have therapeutic potential in COPD.
Authors: Mojtaba Abdul Roda; Amanda M Fernstrand; Frank A Redegeld; J Edwin Blalock; Amit Gaggar; Gert Folkerts Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-04-10 Impact factor: 5.464
Authors: S S Birring; R B Patel; D Parker; S McKenna; B Hargadon; W R Monteiro; J F Falconer Smith; I D Pavord Journal: Thorax Date: 2005-03 Impact factor: 9.139
Authors: Dean Y Maeda; Mark T Quinn; Igor A Schepetkin; Liliya N Kirpotina; John A Zebala Journal: J Pharmacol Exp Ther Date: 2009-09-24 Impact factor: 4.030