leukotriene-b4 and Emphysema

Osteopontin (OPN) is a phosphorylated acidic glycoprotein that can function as both an extracellular matrix molecule and a cytokine. Published data support that OPN is upregulated in surgical lung tissue samples of patients with COPD. The aim of this study was to determine the levels of OPN in sputum supernatants of patients with COPD and to investigate possible associations with mediators and cells involved in the inflammatory and remodeling process as well as with the extent of emphysema.. Seventy-seven patients with COPD and 40 healthy subjects (20 smokers) were studied. All subjects underwent lung function tests, sputum induction for cell count identification, and OPN, transforming growth factor-β1, matrix metalloproteinase (MMP)-2, IL-8, and leukotriene-4 measurement in sputum supernatants. High-resolution CT (HRCT) scan of the chest was performed for quantification of emphysema.. OPN levels (pg/mL) were significantly higher in patients with COPD compared with healthy smokers and nonsmokers (median [interquartile range], 1,340 [601, 6,227] vs 101 [77, 110] vs 68 [50, 89], respectively; P < .001). Regression analysis showed a significant association between OPN and sputum neutrophils, IL-8, MMP-2, and the extent of emphysema. The associations previously listed were not observed in healthy subjects.. OPN levels are higher in patients with COPD compared with healthy subjects. OPN may play a role in the neutrophilic inflammation and in the pathogenesis of emphysema.

Topics: Aged; Emphysema; Female; Humans; Interleukin-8; Leukotriene B4; Male; Matrix Metalloproteinase 2; Middle Aged; Osteopontin; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Sputum; Transforming Growth Factor beta1

The life span of neutrophilic granulocytes has a determining impact on the intensity and duration of neutrophil driven lung inflammation. Based on the compatible solute ectoine, we aimed to prevent anti-apoptotic reactions in neutrophils triggered by the inflammatory microenvironment in the lung. Neutrophils from chronic obstructive pulmonary disease patients and control individuals were exposed to inflammatory mediators and xenobiotics in the presence or absence of ectoine. The in vivo relevance of this approach was tested in xenobiotic-induced lung inflammation in rats. The reduction of apoptosis rates of ex vivo-exposed neutrophils from all study groups was significantly restored in the presence of ectoine. However, natural apoptosis rates not altered by inflammatory stimuli were not changed by ectoine. Mechanistic analyses demonstrated the preventive effect of ectoine on the induction of anti-apoptotic signalling. Neutrophilic lung inflammation induced by single or multiple expositions of animals to environmental particles was reduced after the therapeutic intervention with ectoine. Analyses of neutrophils from bronchoalveolar lavage indicate that the in vivo effect is due to the restoration of neutrophil apoptosis. Ectoine, a compound of the highly compliant group of compatible solutes, demonstrates a reproducible and robust effect on the resolution of lung inflammation.

Topics: Adult; Aged; Amino Acids, Diamino; Animals; Apoptosis; Case-Control Studies; Cells, Cultured; Emphysema; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation; Leukotriene B4; Lung; Male; Middle Aged; Neutrophils; Phosphatidylinositol 3-Kinases; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Inbred F344; Soot; Xenobiotics

To study whether patients with chronic obstructive pulmonary disease (COPD) at the same level of flow limitation but with different clinical phenotypes present different degrees of systemic and/or pulmonary inflammation.. We studied 15 male smokers without COPD (control group) and 39 males with COPD in stable clinical condition. The COPD patients were assigned to 2 groups based on the ratio of carbon monoxide diffusing capacity (DLCO) to alveolar volume (DLCO/VA) expressed as a percentage as follows: a) mainly emphysema (n = 15) and b) mainly chronic bronchitis (n = 24). Classification was determined by comparing both clinical features and diagnostic images.. Mean (SD) concentrations of interleukin 8 (IL-8) and 8-isoprostane in exhaled breath condensate (EBC) were significantly lower in patients with mainly emphysema (IL-8, 0.34 [0.70] pg/mL; 8-isoprostane, 0.07 [0.26] pg/mL) than in patients with chronic bronchitis (IL-8, 2.32 [3.10] pg/mL; 8-isoprostane, 1.77 [2.98] pg/mL) or in the controls (IL-8, 3.14 [4.59] pg/mL; 8-isoprostane, 1.92 [2.84] pg/mL); P < .05 for IL-8 comparisons and P < .01 for 8-isoprostane. IL-8, leukotriene B4, and 8-isoprostano in EBC correlated significantly with DLCO/VA (% of predicted) (r = 0.30, P < .05; r = 0.29, P < or = .05; and r = 0.46, P < .01, respectively) but not with forced expiratory volume in 1 second. There was a negative correlation between EBC and serum levels of both IL-8 (r = -0.31; P < .05) and 8-isoprostane (r = -0.51; P < .001). The correlation between leukotriene B4 concentrations in EBC and serum was not significant, however. No significant differences were found between smokers' and ex-smokers' serum levels of IL-8, leukotriene B4, 8-isoprostane in serum or EBC.. The results indicate that COPD patients with an emphysematous phenotype have a less intense inflammatory response and less oxidative stress in the lung.

Topics: Carbon Monoxide; Diffusion; Dinoprost; Emphysema; Humans; Hydrogen-Ion Concentration; Interleukin-8; Leukotriene B4; Male; Middle Aged; Oxidative Stress; Phenotype; Pneumonia; Pulmonary Disease, Chronic Obstructive; Smoking