Enhanced neutrophil response in chronic obstructive pulmonary disease

Abstract

Background-Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs. Methods-Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 and L-selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNF ). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). 15) v 263 (11); mean diVerence -77 (95% CI of the diVerence -119 to -34), p=0.001). These diVerences were also apparent when patients with COPD were compared with non-smokers (p<0.05). The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation. Results-PatientsConclusions-These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease. (Thorax 2001;56:432-437)

Systemic manifestations and comorbidities of COPD

“…Chemotactic responses to formyl-methionyl-leucyl-phenylalanine and proteolytic activity of circulating neutrophils are increased in patients with emphysema compared with normal smokers and nonsmokers, indicating an abnormality in circulating cells [48]. Neutrophils from COPD patients also show an enhanced production of reactive oxygen species in response to stimulatory agents [49]. Although no difference in spontaneous apoptosis of circulating neutrophils has been reported in COPD patients compared with normal smokers, there is a reduction in L-selectin and an increase in Mac-1 (CD11b) expression [50].…”

Pulmonary vascular changes in asthma and COPD

“…Circulating neutrophils in stable COPD patients appear to have abnormal neutrophil activity with increased production of reactive oxygen radicals. These neutrophils respond stronger to chemotactic factors and attach easier to the endothelial cell layer, which may promote ongoing inflammation and emphysema formation in the lung [99]. In patients with COPD there are an increased number of macrophages in the airways, lung parenchyma and BALf and the numbers of macrophages correlates well with the different GOLD stages of COPD [100].…”

Neutrophilic airway inflammation and IL‐17

“…There is evidence from clinical studies that an exaggerated recruitment and activation of neutrophilic granulocytes in the airways is linked to the clinical course of several inflammatory diseases in the airways and lungs, such as asthma (1)(2)(3)(4)(5)(6)82), nonspecific bronchial hyperreactivity (BHR) (7), chronic bronchitis (3,(8)(9)(10), chronic obstructive pulmonary disease (COPD) (3,(11)(12)(13), cystic fibrosis (14)(15)(16)(17), and acute respiratory distress syndrome (18)(19)(20). The referred evidence has been gathered analysing cellular contents in bronchial tissue, in bronchoalveolar lavage (BAL) fluid, in bronchial biopsies, in induced sputum and in peripheral blood.…”