Jacob Barbara A, Porter Kristi M, Elms Shawn C, Cheng Po-Yung, Jones Dean P, Sutliff Roy L
Department of Pulmonary and Critical Care Medicine, Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Veterans Affairs Medical Center, 1670 Clairmont Rd., Atlanta, GA 30033, USA.
Am J Physiol Lung Cell Mol Physiol. 2006 Oct;291(4):L811-9. doi: 10.1152/ajplung.00468.2005. Epub 2006 May 25.
Human immunodeficiency virus (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 examined the ability of HIV-1 proteins to increase lung oxidative/nitrosative stress after lipopolysaccharide (LPS) (endotoxin) administration in an HIV-1 transgenic mouse model. Lung oxidative/nitrosative stress biomarkers studied 3 and 6 h after LPS administration were as follows: lung edema, tissue superoxide, NO metabolites, nitrotyrosine, hydrogen peroxide, and bronchoalveolar lavage fluid (BALF) glutathione (GSH). Blood serum cytokine levels were quantified to verify immune function of our nonimmunocompromised animal model. Results indicate that 3 h after LPS administration, HIV-1 transgenic mouse lung tissue has significantly greater edema and superoxide. Furthermore, NO metabolites are significantly elevated in HIV-1 transgenic mouse BALF, lung tissue, and blood plasma compared with those of wild-type mice. HIV-1 transgenic mice also produce significantly greater lung nitrotyrosine and hydrogen peroxide than wild-type mice. In addition, HIV-1 transgenic mice produce significantly less BALF GSH than wild-type mice 3 h after LPS treatment. Without treatment, serum cytokine levels are similar for HIV-1 transgenic and wild-type mice. After treatment, serum cytokine levels are significantly elevated in both HIV-1 transgenic and wild-type mice. Therefore, HIV-1 transgenic mice have significantly greater lung oxidative/nitrosative stress after endotoxin administration than wild-type mice, independent of immune function. These results indicate that HIV-1 proteins may increase pulmonary complications subsequent to a secondary infection by altering the lung redox potential.
人类免疫缺陷病毒1型（HIV-1）通过增加宿主对病原体的易感性引发肺部疾病。HIV-1还会导致全身氧化/亚硝化应激增加，这可能会增强继发感染的有害影响。在此，我们在HIV-1转基因小鼠模型中研究了HIV-1蛋白在给予脂多糖（LPS，内毒素）后增加肺部氧化/亚硝化应激的能力。在给予LPS后3小时和6小时研究的肺部氧化/亚硝化应激生物标志物如下：肺水肿、组织超氧化物、NO代谢产物、硝基酪氨酸、过氧化氢以及支气管肺泡灌洗液（BALF）中的谷胱甘肽（GSH）。对血清细胞因子水平进行定量，以验证我们的非免疫受损动物模型的免疫功能。结果表明，给予LPS后3小时，HIV-1转基因小鼠肺组织的水肿和超氧化物水平显著更高。此外，与野生型小鼠相比，HIV-1转基因小鼠的BALF、肺组织和血浆中的NO代谢产物显著升高。HIV-1转基因小鼠产生的肺硝基酪氨酸和过氧化氢也比野生型小鼠显著更多。此外，LPS处理3小时后，HIV-1转基因小鼠产生的BALF GSH比野生型小鼠显著更少。未经处理时，HIV-1转基因小鼠和野生型小鼠的血清细胞因子水平相似。处理后，HIV-1转基因小鼠和野生型小鼠的血清细胞因子水平均显著升高。因此，内毒素给药后，HIV-1转基因小鼠肺部的氧化/亚硝化应激比野生型小鼠显著更大，且与免疫功能无关。这些结果表明，HIV-1蛋白可能通过改变肺氧化还原电位增加继发感染后的肺部并发症。
