Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease

doi:10.1084/jem.176.6.1703

This Article

	Full Text (PDF, 3908K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Genis, P
	Articles by Gendelman, H.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Genis, P
	Articles by Gendelman, H.


Social Bookmarking

	What's this?

ARTICLES

Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease

P Genis, M Jett, EW Bernton, T Boyle, HA Gelbard, K Dzenko, RW Keane, L Resnick, Y Mizrachi, DJ Volsky, LG Epstein, and HE Gendelman
Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307.

Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-1ADA-infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-alpha) and interleukin 1 beta (IL-1 beta) as assayed by coupled reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-beta, IL-1 alpha, IL-6, interferon alpha (IFN-alpha), and IFN-gamma were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV-infected monocytes before coculture reduced, > 2.5-fold, the levels of TNF-alpha. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to- cell interactions between HIV-infected brain macrophages and astrocytes.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Kim, H. J., Martemyanov, K. A., Thayer, S. A. (2008). Human Immunodeficiency Virus Protein Tat Induces Synapse Loss via a Reversible Process That Is Distinct from Cell Death. J. Neurosci. 28: 12604-12613 [Abstract] [Full Text]
Malik, M., Chen, Y.-Y., Kienzle, M. F., Tomkowicz, B. E., Collman, R. G., Ptasznik, A. (2008). Monocyte Migration and LFA-1-Mediated Attachment to Brain Microvascular Endothelia Is Regulated by SDF-1{alpha} through Lyn Kinase. J. Immunol. 181: 4632-4637 [Abstract] [Full Text]
Qiu, H., Straat, K., Rahbar, A., Wan, M., Soderberg-Naucler, C., Haeggstrom, J. Z. (2008). Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells. JEM 205: 19-24 [Abstract] [Full Text]
Wada, K., Arita, M., Nakajima, A., Katayama, K., Kudo, C., Kamisaki, Y., Serhan, C. N. (2006). Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation. FASEB J. 20: 1785-1792 [Abstract] [Full Text]
Persidsky, Y., Heilman, D., Haorah, J., Zelivyanskaya, M., Persidsky, R., Weber, G. A., Shimokawa, H., Kaibuchi, K., Ikezu, T. (2006). Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE). Blood 107: 4770-4780 [Abstract] [Full Text]
McCrossan, M., Marsden, M., Carnie, F. W., Minnis, S., Hansoti, B., Anthony, I. C., Brettle, R. P., Bell, J. E., Simmonds, P. (2006). An immune control model for viral replication in the CNS during presymptomatic HIV infection. Brain 129: 503-516 [Abstract] [Full Text]
Mander, P. K., Jekabsone, A., Brown, G. C. (2006). Microglia Proliferation Is Regulated by Hydrogen Peroxide from NADPH Oxidase. J. Immunol. 176: 1046-1052 [Abstract] [Full Text]
Kim, M.-O., Suh, H.-S., Si, Q., Terman, B. I., Lee, S. C. (2006). Anti-CD45RO Suppresses Human Immunodeficiency Virus Type 1 Replication in Microglia: Role of Hck Tyrosine Kinase and Implications for AIDS Dementia. J. Virol. 80: 62-72 [Abstract] [Full Text]
Dou, H., Ellison, B., Bradley, J., Kasiyanov, A., Poluektova, L. Y., Xiong, H., Maggirwar, S., Dewhurst, S., Gelbard, H. A., Gendelman, H. E. (2005). Neuroprotective Mechanisms of Lithium in Murine Human Immunodeficiency Virus-1 Encephalitis. J. Neurosci. 25: 8375-8385 [Abstract] [Full Text]
Luna-Medina, R., Cortes-Canteli, M., Alonso, M., Santos, A., Martinez, A., Perez-Castillo, A. (2005). Regulation of Inflammatory Response in Neural Cells in Vitro by Thiadiazolidinones Derivatives through Peroxisome Proliferator-activated Receptor {gamma} Activation. J. Biol. Chem. 280: 21453-21462 [Abstract] [Full Text]
Mollace, V., Muscoli, C., Masini, E., Cuzzocrea, S., Salvemini, D. (2005). Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors. Pharmacol. Rev. 57: 217-252 [Abstract] [Full Text]
Kim, B. O., Liu, Y., Zhou, B. Y., He, J. J. (2004). Induction of C Chemokine XCL1 (Lymphotactin/Single C Motif-1{alpha}/Activation-Induced, T Cell-Derived and Chemokine-Related Cytokine) Expression by HIV-1 Tat Protein. J. Immunol. 172: 1888-1895 [Abstract] [Full Text]
Dou, H., Birusingh, K., Faraci, J., Gorantla, S., Poluektova, L. Y., Maggirwar, S. B., Dewhurst, S., Gelbard, H. A., Gendelman, H. E. (2003). Neuroprotective Activities of Sodium Valproate in a Murine Model of Human Immunodeficiency Virus-1 Encephalitis. J. Neurosci. 23: 9162-9170 [Abstract] [Full Text]
Kim, B. O., Liu, Y., Ruan, Y., Xu, Z. C., Schantz, L., He, J. J. (2003). Neuropathologies in Transgenic Mice Expressing Human Immunodeficiency Virus Type 1 Tat Protein under the Regulation of the Astrocyte-Specific Glial Fibrillary Acidic Protein Promoter and Doxycycline. Am. J. Pathol. 162: 1693-1707 [Abstract] [Full Text]
Babas, T., Munoz, D., Mankowski, J. L., Tarwater, P. M., Clements, J. E., Zink, M. C. (2002). Role of Microglial Cells in Selective Replication of Simian Immunodeficiency Virus Genotypes in the Brain. J. Virol. 77: 208-216 [Abstract] [Full Text]
Repovic, P., Benveniste, E. N. (2002). Prostaglandin E2 Is a Novel Inducer of Oncostatin-M Expression in Macrophages and Microglia. J. Neurosci. 22: 5334-5343 [Abstract] [Full Text]
Janabi, N. (2002). Selective Inhibition of Cyclooxygenase-2 Expression by 15-Deoxy-{Delta}12,1412,14-prostaglandin J2 in Activated Human Astrocytes, But Not in Human Brain Macrophages. J. Immunol. 168: 4747-4755 [Abstract] [Full Text]
Ghorpade, A., Persidskaia, R., Suryadevara, R., Che, M., Liu, X. J., Persidsky, Y., Gendelman, H. E. (2001). Mononuclear Phagocyte Differentiation, Activation, and Viral Infection Regulate Matrix Metalloproteinase Expression: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia. J. Virol. 75: 6572-6583 [Abstract] [Full Text]
Pereira, C. F., Boven, L. A., Middel, J., Verhoef, J., Nottet, H. S. L. M. (2000). Induction of cyclooxygenase-2 expression during HIV-1-infected monocyte-derived macrophage and human brain microvascular endothelial cell interactions. J. Leukoc. Biol. 68: 423-428 [Abstract] [Full Text]
Patton, H. K., Zhou, Z.-H., Bubien, J. K., Benveniste, E. N., Benos, D. J. (2000). gp120-induced alterations of human astrocyte function: Na+/H+ exchange, K+ conductance, and glutamate flux. Am. J. Physiol. Cell Physiol. 279: C700-C708 [Abstract] [Full Text]
Grant, R. S., Naif, H., Thuruthyil, S. J., Nasr, N., Littlejohn, T., Takikawa, O., Kapoor, V. (2000). Induction of Indolamine 2,3-Dioxygenase in Primary Human Macrophages by Human Immunodeficiency Virus Type 1 Is Strain Dependent. J. Virol. 74: 4110-4115 [Abstract] [Full Text]
Yeh, M. W., Kaul, M., Zheng, J., Nottet, H. S. L. M., Thylin, M., Gendelman, H. E., Lipton, S. A. (2000). Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of L-Cysteine. J. Immunol. 164: 4265-4270 [Abstract] [Full Text]
Tong, N., Perry, S. W., Zhang, Q., James, H. J., Guo, H., Brooks, A., Bal, H., Kinnear, S. A., Fine, S., Epstein, L. G., Dairaghi, D., Schall, T. J., Gendelman, H. E., Dewhurst, S., Sharer, L. R., Gelbard2, H. A. (2000). Neuronal Fractalkine Expression in HIV-1 Encephalitis: Roles for Macrophage Recruitment and Neuroprotection in the Central Nervous System. J. Immunol. 164: 1333-1339 [Abstract] [Full Text]
Limoges, J., Persidsky, Y., Poluektova, L., Rasmussen, J., Ratanasuwan, W., Zelivyanskaya, M., McClernon, D. R., Lanier, E. R., Gendelman, H. E. (2000). Evaluation of antiretroviral drug efficacy for HIV-1 encephalitis in SCID mice. Neurology 54: 379-379 [Abstract] [Full Text]
Dallasta, L. M., Pisarov, L. A., Esplen, J. E., Werley, J. V., Moses, A. V., Nelson, J. A., Achim, C. L. (1999). Blood-Brain Barrier Tight Junction Disruption in Human Immunodeficiency Virus-1 Encephalitis. Am. J. Pathol. 155: 1915-1927 [Abstract] [Full Text]
Persidsky, Y., Ghorpade, A., Rasmussen, J., Limoges, J., Liu, X. J., Stins, M., Fiala, M., Way, D., Kim, K. S., Witte, M. H., Weinand, M., Carhart, L., Gendelman, H. E. (1999). Microglial and Astrocyte Chemokines Regulate Monocyte Migration through the Blood-Brain Barrier in Human Immunodeficiency Virus-1 Encephalitis. Am. J. Pathol. 155: 1599-1611 [Abstract] [Full Text]
Weiss, J. M., Nath, A., Major, E. O., Berman, J. W. (1999). HIV-1 Tat Induces Monocyte Chemoattractant Protein-1-Mediated Monocyte Transmigration Across a Model of the Human Blood-Brain Barrier and Up-Regulates CCR5 Expression on Human Monocytes. J. Immunol. 163: 2953-2959 [Abstract] [Full Text]
Nath, A., Conant, K., Chen, P., Scott, C., Major, E. O. (1999). Transient Exposure to HIV-1 Tat Protein Results in Cytokine Production in Macrophages and Astrocytes. A HIT AND RUN PHENOMENON. J. Biol. Chem. 274: 17098-17102 [Abstract] [Full Text]
Ensoli, F., Fiorelli, V., DeCristofaro, M., Santini Muratori, D., Novi, A., Vannelli, B., Thiele, C. J., Luzi, G., Aiuti, F. (1999). Inflammatory Cytokines and HIV-1-Associated Neurodegeneration: Oncostatin-M Produced by Mononuclear Cells from HIV-1-Infected Individuals Induces Apoptosis of Primary Neurons. J. Immunol. 162: 6268-6277 [Abstract] [Full Text]
Colasanti, M., Persichini, T., Cavalieri, E., Fabrizi, C., Mariotto, S., Menegazzi, M., Lauro, G. M., Suzuki, H. (1999). Rapid Inactivation of NOS-I by Lipopolysaccharide Plus Interferon-gamma -induced Tyrosine Phosphorylation. J. Biol. Chem. 274: 9915-9917 [Abstract] [Full Text]
Boven, L. A., Gomes, L., Hery, C., Gray, F., Verhoef, J., Portegies, P., Tardieu, M., Nottet, H. S. L. M. (1999). Increased Peroxynitrite Activity in AIDS Dementia Complex: Implications for the Neuropathogenesis of HIV-1 Infection. J. Immunol. 162: 4319-4327 [Abstract] [Full Text]
Harrison, M J G, Newman, S P, Hall-Craggs, M A, Fowler, C J, Miller, R, Kendall, B E, Paley, M, Wilkinson, I, Sweeney, B, Lunn, S, Carter, S, Williams, I (1998). Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study. J. Neurol. Neurosurg. Psychiatry 65: 301-307 [Abstract] [Full Text]
Perry, S. W., Hamilton, J. A., Tjoelker, L. W., Dbaibo, G., Dzenko, K. A., Epstein, L. G., Hannun, Y., Whittaker, J. S., Dewhurst, S., Gelbard, H. A. (1998). Platelet-activating Factor Receptor Activation. AN INITIATOR STEP IN HIV-1 NEUROPATHOGENESIS. J. Biol. Chem. 273: 17660-17664 [Abstract] [Full Text]
Tan, S V, Guiloff, R J (1998). Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS. J. Neurol. Neurosurg. Psychiatry 65: 23-28 [Abstract] [Full Text]
Heyes, M. P., Saito, K., Lackner, A., Wiley, C. A., Achim, C. L., Markey, S. P. (1998). Sources of the neurotoxin quinolinic acid in the brain of HIV-1-infected patients and retrovirus-infected macaques. FASEB J. 12: 881-896 [Abstract] [Full Text]
Yu, N., Billaud, J. N., Phillips, T. R. (1998). Effects of feline immunodeficiency virus on astrocyte glutamate uptake: Implications for lentivirus-induced central nervous system diseases. Proc. Natl. Acad. Sci. USA 95: 2624-2629 [Abstract] [Full Text]
Chen, P., Mayne, M., Power, C., Nath, A. (1997). The Tat Protein of HIV-1 Induces Tumor Necrosis Factor-alpha Production. IMPLICATIONS FOR HIV-1-ASSOCIATED NEUROLOGICAL DISEASES. J. Biol. Chem. 272: 22385-22388 [Abstract] [Full Text]
Mitola, S., Sozzani, S., Luini, W., Primo, L., Borsatti, A., Weich, H., Bussolino, F. (1997). Tat-Human Immunodeficiency Virus-1 Induces Human Monocyte Chemotaxis by Activation of Vascular Endothelial Growth Factor Receptor-1. Blood 90: 1365-1372 [Abstract] [Full Text]
Takano, T., Fiore, S., Maddox, J. F., Brady, H. R., Petasis, N. A., Serhan, C. N. (1997). Aspirin-triggered 15-Epi-Lipoxin A4 (LXA4) and LXA4 Stable Analogues Are Potent Inhibitors of Acute Inflammation: Evidence for Anti-inflammatory Receptors. JEM 185: 1693-1704 [Abstract] [Full Text]
Colasanti, M., Cavalieri, E., Persichini, T., Mollace, V., Mariotto, S., Suzuki, H., Lauro, G. M. (1997). Bacterial Lipopolysaccharide Plus Interferon-gamma Elicit a Very Fast Inhibition of a Ca2+-dependent Nitric-oxide Synthase Activity in Human Astrocytoma Cells. J. Biol. Chem. 272: 7582-7585 [Abstract] [Full Text]
Adamson, D. C., Wildemann, B., Sasaki, M., Glass, J. D., McArthur, J. C., Christov, V. I., Dawson, T. M., Dawson, V. L. (1996). Immunologic NO Synthase: Elevation in Severe AIDS Dementia and Induction by HIV-1 gp41. Science 274: 1917-1921 [Abstract] [Full Text]
Fine, S. M., Angel, R. A., Perry, S. W., Epstein, L. G., Rothstein, J. D., Dewhurst, S., Gelbard, H. A. (1996). Tumor Necrosis Factor alpha Inhibits Glutamate Uptake by Primary Human Astrocytes. IMPLICATIONS FOR PATHOGENESIS OF HIV-1 DEMENTIA. J. Biol. Chem. 271: 15303-15306 [Abstract] [Full Text]
Mori, M., Aihara, M., Kume, K., Hamanoue, M., Kohsaka, S., Shimizu, T. (1996). Predominant Expression of Platelet-Activating Factor Receptor in the Rat Brain Microglia. J. Neurosci. 16: 3590-3600 [Abstract] [Full Text]
Giulian, D., Yu, J., Li, X., Tom, D., Li, J., Wendt, E., Lin, S.-N., Schwarcz, R., Noonan, C. (1996). Study of Receptor-Mediated Neurotoxins Released by HIV-1-Infected Mononuclear Phagocytes Found in Human Brain. J. Neurosci. 16: 3139-3153 [Abstract] [Full Text]
Colasanti, M., Persichini, T., Menegazzi, M., Mariotto, S., Giordano, E., Caldarera, C. M., Sogos, V., Lauro, G. M., Suzuki, H. (1995). Induction of Nitric Oxide Synthase mRNA Expression. J. Biol. Chem. 270: 26731-26733 [Abstract] [Full Text]
Mintz, M. (1995). Carnitine in Human Immunodeficiency Virus Type 1 Infection/Acquired Immune Deficiency Syndrome. J Child Neurol 10: 2S40-2S44 [Abstract]
Lipton, S. A., Gendelman, H. E. (1995). Dementia Associated with the Acquired Immunodeficiency Syndrome. NEJM 332: 934-940 [Full Text]