RESUMEN
BACKGROUND: Acquired somatic mutations induced by oxidative stress may contribute to the molecular pathogenesis of chronic inflammatory airway diseases. The objective of this study was to assess the intensity of oxidative DNA damage and the presence of microsatellite DNA instability (MSI), a marker of acquired somatic mutations, in patients with COPD, patients with noncystic fibrosis bronchiectasis, and control subjects. METHODS: Induced sputum and peripheral blood from 97 subjects were analyzed; 36 patients with COPD, 36 patients with bronchiectasis, 15 smokers without COPD, and 10 healthy control subjects. DNA was extracted and analyzed for MSI. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a specific marker of oxidant-induced DNA damage, was measured in serum and sputum supernatants. RESULTS: None of the patients with bronchiectasis or control subjects (non-COPD smokers, healthy subjects) exhibited any genetic alteration. In contrast, MSI was found in 38% of COPD specimens. Sputum 8-OHdG was statistically significantly increased in COPD when compared with subjects with bronchiectasis (P = .0002), smokers without COPD (P = .0056), and healthy subjects (P = .0003). Sputum 8-OHdG in MSI-positive patients with COPD differed significantly from that of MSI-negative patients with COPD (P = .04) and smokers without COPD (P = .008), but was not statistically different (P = .07) among MSI-negative patients with COPD and smokers without COPD. Serum 8-OHdG was significantly increased in MSI-positive compared with MSI-negative patients with COPD (P = .001), but was not statistically significant in smokers without COPD (P = .09). Serum 8-OHdG was increased in smokers without COPD compared with MSI-negative patients with COPD (P = .009). CONCLUSIONS: There is a clear disparity in COPD regarding oxidant-induced DNA damage and somatic mutations. This may reflect a difference in the oxidative stress per se or a deficient antioxidant and/or repair capacity in the lungs of patients with COPD.
Asunto(s)
Bronquiectasia/genética , Daño del ADN/genética , Análisis Mutacional de ADN , Inestabilidad de Microsatélites , Estrés Oxidativo/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Fibrosis Pulmonar/genética , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Mediciones del Volumen Pulmonar , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores de Riesgo , Fumar/efectos adversos , EspirometríaRESUMEN
BACKGROUND: New lymphatic vessels are associated with tissue injury and repair. Recent studies have shown increased lymphatic follicles formation in the lungs of COPD patients. We hypothesized that lymphatic vascular remodeling could be part of COPD pathogenesis. AIM: To investigate the lymphangiogenetic process in COPD we measured the lymphatic microvessel density (LMVD), the lymphatic invasion (L.I), and their correlation with clinical and laboratory parameters. METHODS: Lung tissue from 20 COPD patients and 20 non-COPD smokers was immunohistochemically stained for D2-40 (lymphatic endothelial cell marker), and LYVE-1 (lymphatic endothelial hyaluronan receptor 1). Both groups had similar age and smoking history. RESULTS: D2-40 and LYVE-1 were expressed in all specimens. Lymphatic invasion was presented only in COPD specimens. Lymphatic microvessel density (LMVD) as revealed by D2-40 and LYVE-1 markers was statistically significantly higher in COPD patients when compared with non-COPD smokers. Both markers (D2-40, LYVE-1) were correlated with FEV1 (% pred) (R(2) = 0.415, R(2) = 0.605, respectively). CONCLUSIONS: We report for the first time high lymphatic microvessel density and lymphatic invasion in COPD patients, related to the degree of airway obstruction. Our findings could provide novel insights in the pathogenesis of the disease.
