ArticleAmerican journal of respiratory cell and molecular biology2008
HIV-1-transgene expression in rats decreases alveolar macrophage zinc levels and phagocytosis.
Article in American journal of respiratory cell and molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.International journal of molecular sciences · 2025Review
- The role of alveolar macrophages in viral respiratory infections and their therapeutic implications.Biochemistry and biophysics reports · 2024Review
- HIV-associated lung disease.Nature reviews. Disease primers · 2023Review
- Granulocyte Macrophage-Colony Stimulating Factor Reverses HIV Protein-Induced Mitochondrial Derangements in Alveolar Macrophages.AIDS research and human retroviruses · 2021Article
- HIV Impairs Alveolar Macrophage Function via MicroRNA-144-Induced Suppression of Nrf2.The American journal of the medical sciences · 2021Article
- MiR-144 mediates Nrf2 inhibition and alveolar epithelial dysfunction in HIV-1 transgenic rats.American journal of physiology. Cell physiology · 2019Article
- The Role of Zinc and Zinc Homeostasis in Macrophage Function.Journal of immunology research · 2018Review
- Therapeutic Modulation of Virus-Induced Oxidative Stress via the Nrf2-Dependent Antioxidative Pathway.Oxidative medicine and cellular longevity · 2018Review
- Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβAIDS research and human retroviruses · 2017Article
- HIV-1 decreases Nrf2/ARE activity and phagocytic function in alveolar macrophages.Journal of leukocyte biology · 2017Article
- Pulmonary Innate Immune Dysfunction in Human Immunodeficiency Virus.American journal of respiratory cell and molecular biology · 2017Review
- HIV-related proteins prolong macrophage survival through induction of Triggering receptor expressed on myeloid cells-1.Scientific reports · 2017Article
- Effect of Cocaine on Pulmonary Vascular Remodeling and Hemodynamics in Human Immunodeficiency Virus-Transgenic Rats.American journal of respiratory cell and molecular biology · 2016Article
- Characterization of neuropathology in the HIV-1 transgenic rat at different ages.Journal of neuroimmunology · 2016Article
- The HIV-1 transgenic rat model of neuroHIV.Brain, behavior, and immunity · 2015Review
- Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages.AIDS research and human retroviruses · 2015Article
- Noninfectious pulmonary complications of human immunodeficiency virus infection.The American journal of the medical sciences · 2014Review
- The complexity of HIV persistence and pathogenesis in the lung under antiretroviral therapy: challenges beyond AIDS.Viral immunology · 2014Review
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
HIV-1 infection impairs alveolar macrophage immune function and renders patients susceptible to pneumonia by poorly understood mechanisms. Alveolar macrophage maturation and function depends on granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced and secreted by the alveolar epithelium. Macrophages respond to GM-CSF through the GM-CSF receptor (GM-CSFR), which has a binding subunit (GM-CSFRalpha) and a signaling subunit (GM-CSFRbeta). In this study, we measured GM-CSFR expression and alveolar macrophage function in a transgene HIV-1 rat model (NL4-3Delta gag/pol); this construct bears a pro-virus with gag and pol deleted, but other HIV-1-related proteins, such as gp120 and Tat, are expressed, and the rats develop an AIDS-like phenotype as they age. We first determined that HIV-1-transgenic expression selectively decreased alveolar macrophage expression of GM-CSFRbeta and impaired bacterial phagocytosis in vitro. Next, we examined the role of zinc (Zn) deficiency as a potential mechanism underlying these effects, and determined that HIV-1-transgenic rats have significantly lower levels of Zn in the alveolar space and macrophages. To test the direct effect of Zn deficiency on macrophage dysfunction, we treated rat alveolar macrophage cell line with a Zn chelator, N,N,N',N'-tetrakis-(2-pyridyl-methyl) ethylenediamine, and this decreased GM-CSFRbeta expression and phagocytosis. In parallel, treatment with Zn acetate in vitro for 48 hours restored intracellular Zn levels and phagocytic function in alveolar macrophages from HIV-1-transgenic rats. Taken together, these data suggest that pulmonary Zn deficiency could be one of the mechanisms by which chronic HIV-1 infection impairs alveolar macrophage immune function and renders these individuals susceptible to serious lung infections.
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