Background: Oxidative stress has been suggested in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) with an additional burden of diabetes, hypertension and cardiovascular disease. In the present study, we investigated erythrocyte antioxidant enzymes activities in correlation to COPD severity and COPD comorbidities. Methods: One hundred twenty seven subjects with COPD and 59 healthy controls participated in this study. COPD severity was done based on the Global Initiative for Chronic Obstructive Lung Disease criteria. The erythrocytes enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and total antioxidant status (TAS) were measured with spectrophotometric method. Results: COPD patients showed significant decrease in TAS (p > 0.05), GST (p < 0.001) and GPx (p < 0.01) activities with progression of the disease. In patients, FEV 1 was negatively correlated with SOD, GR and positively correlated with GST and GPx activities. Further, multivariate logistic regression analysis revealed GST (OR = 0.93; 95% CI = -0.10 -0.01; p < 0.01) , GPx (OR = 0.98; 95% CI = -0.03 -0.00; p < 0.05) and TAS (OR = 0.95; 95% CI = -0.08 -0.00; p < 0.05) were independently associated with FEV 1 in GOLD stage IV and GST (OR = 1.11; 95% CI = 0.04-0.18; p < 0.001) in GOLD stage II. Regression analysis confirmed a significant difference in GPx activity in COPD -type 2 diabetes (OR = 0.04; 95% CI = -6.60 -0.53; P = 0.09), and GST activity in COPD -cardiovascular disease (OR = 2.51; 95% CI = 0.00 -1.84; p < 0.05) patients when compared to patients without comorbidities. Conclusion: A significant decline in lung function may be associated with altered antioxidant enzyme activity due to the strong correlation between GST and GPx with COPD severity. Our results also indicate that erythrocytes GST and GPX activities are significantly associated with comorbidities, but only in COPD patients with type 2 diabetes and cardiovascular disease.

ICAM-1 is required for firm adhesion of leukocytes to the endothelium. However, how the spatial organization of endothelial ICAM-1 regulates leukocyte adhesion is not well understood. In this study, we identified the calcium-effector protein annexin A2 as a novel binding partner for ICAM-1. ICAM-1 clustering promotes the ICAM-1–annexin A2 interaction and induces translocation of ICAM-1 into caveolin-1–rich membrane domains. Depletion of endothelial annexin A2 using RNA interference enhances ICAM-1 membrane mobility and prevents the translocation of ICAM-1 into caveolin-1–rich membrane domains. Surprisingly, this results in increased neutrophil adhesion and transendothelial migration under flow conditions and reduced crawling time, velocity, and lateral migration distance of neutrophils on the endothelium. In conclusion, our data show that annexin A2 limits neutrophil transendothelial migration by organizing the spatial distribution of ICAM-1.

Identification of biomarkers for the novel therapeutics targets of Chronic obstructive pulmonary disease (COPD) is an important area of current research. In this study, the level of inflammatory cytokines was investigated and correlated these levels with erythrocytic antioxidant activities in COPD patients with smokers and without smokers and parameters of severity. Material and Methods: Plasma levels of Interleukin (IL)-6, IL-8 and IL-10 concentrations were assayed by means of Enzyme-linked Immunosorbent Assay (ELISA) and erythrocytic glutathione-stransferase (GST) and glutathione peroxidase (GPx) activities were estimated by spectrophotometric method. Results: Both IL-6 and IL-8 plasma levels showed a statistically significantly higher in COPD patients as compared to healthy controls (p<0.001; p<0.05). In contrast, the IL-10 was lower in COPD patients as compared to control group (p<0.05). FEV1 was significantly negatively correlated with plasma IL-6 (r= -0.565, p< 0.001) and IL-8 (r= -0.453, p <0.05). Plasma IL-6 was found negative association with erythrocytic GST (r= -0.018, p>0.05) and GPx activities (r= -0.080, p>0.05). Similarly IL-8 was also found negative association with GST (r= -0.260, p>0.05) and GPx activities (r= -0.268, p>0.05). Whereas, a significant positive association was observed between IL-10 and erythrocytic GST (r= 0.494, p <0.05) and GPx activities (r= 0.546, p < 0.001). Conclusion:In conclusion, Plasma levels of inflammatory cytokines IL-6 and IL-8 are related with severity of COPD and IL-10 and oxidative stress markers GST and GPx are co-dependent and strongly interrelated processes and may be used as a potential marker for the evaluation of COPD.