Nitric Oxide Regulates MIP-1α Expression in Primary Macrophages and T Lymphocytes: Implications for Anti-HIV-1 Response
Article
Sherry, B, Schmidtmayerova, H, Zybarth, G et al. (2000). Nitric Oxide Regulates MIP-1α Expression in Primary Macrophages and T Lymphocytes: Implications for Anti-HIV-1 Response
. 6(6), 542-549. 10.1007/BF03401793
Sherry, B, Schmidtmayerova, H, Zybarth, G et al. (2000). Nitric Oxide Regulates MIP-1α Expression in Primary Macrophages and T Lymphocytes: Implications for Anti-HIV-1 Response
. 6(6), 542-549. 10.1007/BF03401793
Background: Chemokines and chemokine receptors have been shown to play a critical role in HIV infection. Chemokine receptors have been identified as coreceptors for viral entry into susceptible target cells, and several members of the β chemokine subfamily of cytokines, MIP-1α, MIP-1β, and RANTES, have been identified as the major human immunodeficiency virus (HIV)-suppressive factors produced by activated CD8+ T lymphocytes. In macrophages, HIV-1 infection itself was shown to upregulate the production of MIP-1α and MIP-1β. In the present study, we address the mechanisms by which HIV-1 infection regulates β chemokine responses in macrophages and lymphocytes. Material and Methods: To address whether nitric oxide (NO), generated as a consequence of HIV-1 infection, regulates β chemokine responses in monocyte/macrophages and/or macrophage-depleted peripheral blood mononuclear cells (PBMCs) these two cell populations were isolated from HIV seronegative donors, placed in culture, and infected with HIV-1 in either the presence or absence of exogenous activators (e.g. lipopolysaccharide, phytohemagglutinin), inhibitors of nitric oxide synthase (NOS), or chemical donors of NO. Cultures were analyzed for β chemokine responses by ELISA and RNase protection. Results: LPS-induced MIP-1α release is enhanced in HIV-1-infected, as compared to uninfected, monocyte/macrophage cultures, and this enhancing effect is partially blocked by the addition of inhibitors of NOS, and can be reproduced by chemical generators of NO even in the absence of HIV-1 infection. A similar strategy was used to demonstrate a role for NO in HIV-1-mediated induction of MIP-1α in unstimulated macrophage cultures. NOS inhibitors also decreased MIP-1α and MIP-1β production by phytohemagglutinin-stimulated monocyte-depleted PBMC cultures. Conclusions: These results indicate that NO amplifies MIP-1α responses in activated macrophages and lymphocytes, and suggests that this pleiotropic molecule might function as an enhancing signal that regulates secretion of β chemokines during HIV-1 infection. These findings reveal a novel mechanism by which NO might regulate the anti-HIV activity of immune cells.
