HIV‐1 Induced Pulmonary Oxidative and Nitrosative Stress: Exacerbated Response to Endotoxin Administration in an HIV‐1 Transgenic Mouse Model

Abstract

HIV-1 causes lung disease by increasing the host's susceptibility to pathogens. HIV-1 also causes an increase in systemic oxidative/nitrosative stress, perhaps enhancing the deleterious effects of secondary infections. Here, we have examined the ability of HIV-1 proteins to increase lung oxidative/nitrosative stress following lipopolysaccaride (LPS) administration in an HIV-1 transgenic mouse model. Lung oxidative/nitrosative stress biomarkers studied 3 and 6 hours post LPS administration were as follows; lung edema, tissue superoxide, nitrotyrosine, and hydrogen peroxide, bronchoalveolar lavage fluid glutathione (GSH), and nitrosoglutathione. Results indicate that, 3 hours post LPS administration, HIV-1 transgenic mice lung tissue shows greater lung edema and staining for superoxide and nitrotyrosine compared to wild type mice. HIV-1 transgenic mice produce significantly greater lung hydrogen peroxide in comparison to wild type mice. HIV-1 transgenic mice also produce significantly less GSH in comparison to wild type 3 hours post LPS treatment. Nitrosoglutathione levels were significantly lower in HIV-1 transgenic mice than in wild type 3 hours post LPS administration. Therefore, HIV-1 transgenic mice have significantly greater lung oxidative/nitrosative stress than wild type mice following LPS administration, perhaps predisposing these mice to greater lung complications subsequent to a secondary infection.