Superoxide production by peripheral polymorphonuclear leukocytes in patients with COPD

Abstract

Polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of COPD, partly because of the release of oxidants, like superoxide anion (SA). The goal of this study was to measure the spontaneous and stimulated release of SA by peripheral PMN in stable COPD compared with healthy controls. Seventeen patients with stable moderate COPD and 17 healthy age-matched controls were included. SA release from peripheral PMN was measured spectrophotometrically as the superoxide dismutase (SOD) inhibitable reduction of cytochrome c. PMNs were stimulated with phorbol myristate acetate (PMA, 1 and 10 ng/ml), diesel exhaust particles (DEPs), carbon black (CB) and ultrafine CB (ufCB, 125, 250 and 500 microg/ml). The spontaneous SA release (PMA-0) between patients and control subjects was not significantly different. After stimulation with PMA, SA release increased in both patients and controls. The SA release did not increase after stimulation with DEP and CB in patients nor in controls. There was only an increase after stimulation with ufCB in the patient group. The increased SA release in COPD patients after stimulation with ufCB may suggest that PMN of COPD patients are more prone to stimulation and that the smaller particle size of ufCB might be a crucial factor.

Increased production of hydrogen peroxide by peripheral blood monocytes associated with smoking exposure intensity in smokers

“…Our results are also in agreement with those of Ishida et al [24], who identified higher H 2 O 2 production in alveolar macrophage cultures of rats exposed to cigarette smoke. In contrast to our results, van Beurden et al [14] did not detect differences in the release of superoxide dismutase by PBM cultures, either spontaneously or after stimulation with PMA, between COPD current/ex-smoker patients and healthy controls, and the smoking history did not influence the results when compared by covariance analysis between groups. The authors concluded that superoxide dismutase is only one of the oxidants that are produced by PBM culture; these cells also produce H 2 O 2 and hydroxyl radicals.…”

“…The main finding was that the smokers exhibited significantly higher secretion of H 2 O 2 than the healthy controls and that there was a significantly positive association of oxidative stress with pack-years of smoking. These results confirm that smoking itself is an important determinant of oxidative stress and that a higher consumption of cigarettes is associated with higher levels of oxidative stress [12,14,20]. We also reinforce previous findings that smokers exhibit evidence of systemic inflammation compared with healthy controls [7,21].…”

“…In the study of van Beurden et al [14], the production of superoxide by PMNs was not associated with the intensity of smoking exposure evaluated by smoking history duration. Similarly, Yeh et al [15] did not find an association with smoking history duration when protein carbonylation was used as a biomarker for oxidative stress.…”

SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects

“…The irritants activate pulmonary macrophages that secrete cytokines, such as IL-8 and Gro-a, which attract and activate neutrophils [3,21]. The neutrophils recruited to the site of inflammation release enzymes, such as elastase, lysozymes and myeloperoxidase [3], and microcidal superoxides are generated at the cell surface of the neutrophils [22]. In addition, neutrophils themselves release IL-8.…”

A synthetic, non-peptide CXCR2 antagonist blocks MIP-2-induced neutrophil migration in mice

“…However, massive infiltration of neutrophils leads to tissue damage and sustains inflammation due to the release of reactive oxygen intermediates (ROI), proteinases and immunomodulatory cytokines. In addition, neutrophils are thought to play a critical role in severe chronic diseases like inflammatory bowel disease, rheumatoid arthritis and chronic obstructive pulmonary disease (Elford and Cooper, 1991;Papadakis and Targan, 2000;van Beurden et al, 2003).…”