Recent studies show that endogenous hydrogen sulfide (H(2)S) plays an anti-inflammatory role in the pathogenesis of airway inflammation. This study investigated whether exogenous H(2)S may counteract oxidative stress-mediated lung damage in allergic mice. Female BALB/c mice previously sensitized with ovalbumin (OVA) were treated with sodium hydrosulfide (NaHS) 30 min before OVA challenge. Forty eight hours after antigen-challenge, the mice were killed and leukocyte counting as well as nitrite plus nitrate concentrations were determined in the bronchoalveolar lavage fluid, and lung tissue was analysed for nitric oxide synthase (NOS) activity, iNOS expression, superoxide dismutase (SOD), catalase, glutathione reductase (GR) and glutathione peroxidase (GPx) activities, thiobarbituric acid reactive species and 3-nitrotyrosine containing proteins (3-NT). Pre-treatment of OVA-sensitized mice with NaHS resulted in significant reduction of both eosinophil and neutrophil migration to the lungs, and prevented the elevation of iNOS expression and activity observed in the lungs from the untreated allergic mice, although it did not affect 3-NT. NaHS treatment also abolished the increased lipid peroxidation present in the allergic mouse lungs and increased SOD, GPx and GR enzyme activities. These results show, for the first time, that the beneficial in vivo effects of the H(2)S-donor NaHS on allergic airway inflammation involve its inhibitory action on leukocyte recruitment and the prevention of lung damage by increasing endogenous antioxidant defenses. Thus, exogenous administration of H(2)S donors may be beneficial in reducing the deleterius impact of allergic pulmonary disease, and might represent an additional class of pharmacological agents for treatment of chronic pulmonary diseases.

Although numerous studies demonstrate the participation of nitric oxide (NO) in various inflammatory diseases, the precise function of NO in allergic asthma remains unclear. We investigated whether iNOS inhibition could interfere with the kinetics of VLA-4 and Mac-1 expression and adhesion properties of bone marrow and peripheral blood eosinophils of sensitized mice after antigen exposure. Treatment of allergic mice with 1400 W (iNOS inhibitor) increased the adhesion of bone marrow eosinophils to ICAM-1, but not blood eosinophils, at 24h and 48 h after OVA-challenge. Conversely, adhesion of blood eosinophils from 1400 W-treated mice to VCAM-1 diminished at 24h and was almost completely blocked at 48 h. 1400 W did not induce any change in the adhesion of bone marrow eosinophils to VCAM-1, at 24h, but cells collected 48 h after challenge showed significantly lower adherence. Flow cytometry demonstrated that 1400 W resulted in a significantly increased Mac-1 expression on bone marrow eosinophils at 24h, as compared to control mice. However, at 24h, 1400 W significantly decreased Mac-1 and VLA-4 expressions on blood eosinophils. At 48 h, the expressions of both Mac-1 and VLA-4 returned to previous levels. Results show a temporal effect of iNOS upon Mac-1 expression and function, the chief adhesion molecule involved in the eosinophil efflux from the bone marrow at 24h. In contrast, Mac-1 and VLA-4 were involved in eosinophil mobilization from blood to lungs at 48 h after antigen challenge. Data suggest an important role of the Mac-1 and VLA-4 in the iNOS-modulated migration of eosinophils to the lungs of allergic mice.

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