The macrophage in the persistence and pathogenesis of HIV infection

Gendelman, Howard Eliot; Orenstein, Jan M.; Baca, L M; Weiser, Barbara; Burger, Harold; Kalter, Debra Chester; Meltzer, Monte S.

doi:10.1097/00002030-198908000-00001

Cited by 346 publications

(204 citation statements)

References 0 publications

Supporting

Mentioning

195

Contrasting

Unclassified

Order By: Relevance

“…After 24-48 h, MDM were infected with HIV-1 ADA , as previously described (12). HIV-1 ADA was obtained through the AIDS Research and Reference Reagent Program (ARRRP), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), from Dr. H. Gendelman (17,18), then expanded in human monocytes before purification by ultracentrifugation (Advanced Biotechnologies, Columbia, MD). Every 3 days thereafter, 80% of the culture medium was collected, stored at Ϫ80 o , then replaced.…”

Section: Monocyte Isolation and Culturementioning

confidence: 99%

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Kutza

Crim

Feldman

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Macrophages infected with HIV-1 produce high levels of M-CSF and macrophage-inflammatory protein-1α (MIP-1α). M-CSF facilitates the growth and differentiation of macrophages, while the chemotactic properties of MIP-1α attract both T lymphocytes and macrophages to the site of HIV infection. Studies described in this work indicate M-CSF may function in an autocrine/paracrine manner to sustain HIV replication, and data suggest possible therapeutic strategies for decreasing viral load following HIV infection. We show that macrophage infection with measles virus or respiratory syncytial virus, in contrast to HIV-1, results in production of MIP-1α, but not M-CSF. Thus, M-CSF appears to be specifically produced upon infection of macrophages with HIV-1. Furthermore, addition of M-CSF antagonists to HIV-1-infected macrophages, including anti-M-CSF monoclonal or polyclonal Abs or soluble M-CSF receptors, dramatically inhibited HIV-1 replication and reduced production of MIP-1α. Our results suggest that biologic antagonists for M-CSF may represent novel strategies for inhibiting the spread of HIV-1 by 1) blocking virus replication in macrophages, 2) reducing recruitment of HIV-susceptible T cells and macrophages by MIP-1α, and 3) preventing the establishment and maintenance of infected macrophages as a reservoir for HIV.

show abstract

Section: Monocyte Isolation and Culturementioning

confidence: 99%

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Kutza

Crim

Feldman

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Thus, they are major reservoirs for HIV during all stages of the disease and represent an efficient vector for viral dissemination throughout the body (3). The replication of HIV in tissue macrophages has been associated with clinical manifestations, including encephalopathy (1). Macrophages are also targets for opportunistic infections such as herpes virus type 1 or Mycobacterium tuberculosis during the course of HIV disease (4).…”

Section: Retrovirally Mediated Ifn-␤ Transduction Of Macrophagesmentioning

confidence: 99%

Retrovirally Mediated IFN-β Transduction of Macrophages Induces Resistance to HIV, Correlated with Up-Regulation of RANTES Production and Down-Regulation of C-C Chemokine Receptor-5 Expression

Cremer

Vieillard

Maeyer

2000

The Journal of Immunology

View full text Add to dashboard Cite

Constitutive expression of IFN-β by HIV target cells may be an alternative or complementary therapeutic approach for the treatment of AIDS. We show that macrophages derived from CD34+ cells from umbilical cord blood can be efficiently transduced by a retroviral vector carrying the IFN-β coding sequence. This results in resistance to infection by a macrophage-tropic HIV type 1, as shown by the drastic reduction in the HIV DNA copy number per cell and in p24 release. Moreover, IFN-β transduction totally blocked secretion of proinflammatory cytokines after HIV infection. The constitutive IFN-β production also resulted in an increased production of IL-12 and IFN-γ Th1-type cytokines and of the β-chemokines macrophage-inflammatory protein-1α, macrophage-inflammatory protein-1β, and RANTES. RANTES was found to be involved in the HIV resistance observed, and this was correlated with a down-regulation of the CCR-5 HIV entry coreceptor. These results demonstrate the feasibility and the efficacy of such IFN-β-mediated gene therapy. In addition to inhibiting HIV replication, IFN-β transduction could have beneficial immune effects in HIV-infected patients by favoring cellular immune responses.

show abstract

“…Microglial cells rapidly respond to insults with hypertrophy, proliferation, and expression of proinflammatory cytokines [48]. Indeed, in neurodegenerative diseases, activated microglia affect neuronal injury through secretion of glutamate, proinflammatory factors, reactive oxygen species, quinolinic acid amongst others and by mobilization of adaptive immune responses and cell chemotaxis leading to transendothelial immune cell migration across the BBB and perpetuation of neural damage [49][50][51][52]. As disease progresses, inflammatory secretions engage neighboring glial cells, including astrocytes and endothelial cells, resulting in a vicious cycle of autocrine and paracrine amplification of inflammation resulting in significant tissue injury and deficits in neurogenesis [53].…”

Section: Neurodegenerative Disordersmentioning

confidence: 99%

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

Kabanov

Gendelman

2007

Progress in Polymer Science

229

138

View full text Add to dashboard Cite

Neurodegenerative and infectious disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population's age. Alzheimer's disease alone currently affects 4.5 million Americans, and more than $100 billion is spent per year on medical and institutional care for affected people. Such numbers will double in the ensuing decades. Currently disease diagnosis for all disorders is made, in large measure, on clinical grounds as laboratory and neuroimaging tests confirm what is seen by more routine examination. Achieving early diagnosis would enable improved disease outcomes. Drugs, vaccines or regenerative proteins present "real" possibilities for positively affecting disease outcomes, but are limited in that their entry into the brain is commonly restricted across the blood-brain barrier. This review highlights how these obstacles can be overcome by polymer science and nanotechnology. Such approaches may improve diagnostic and therapeutic outcomes. New developments in polymer science coupled with cell-based delivery strategies support the notion that diseases that now have limited therapeutic options can show improved outcomes by advances in nanomedicine.

show abstract

The macrophage in the persistence and pathogenesis of HIV infection

Cited by 346 publications

References 0 publications

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Retrovirally Mediated IFN-β Transduction of Macrophages Induces Resistance to HIV, Correlated with Up-Regulation of RANTES Production and Down-Regulation of C-C Chemokine Receptor-5 Expression

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

Contact Info

Product

Resources

About