Affordable Access

deepdyve-link
Publisher Website

Granulocyte Macrophage-Colony Stimulating Factor Reverses HIV Protein-Induced Mitochondrial Derangements in Alveolar Macrophages.

Authors
  • Staitieh, Bashar S1
  • Auld, Sara C1, 2
  • Ahmed, Mariam1
  • Fan, Xian1
  • Smirnova, Natalia1
  • Yeligar, Samantha M1, 3
  • 1 Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. , (Georgia)
  • 2 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. , (Georgia)
  • 3 Atlanta VA Health Care System, Decatur, Georgia, USA. , (Georgia)
Type
Published Article
Journal
AIDS Research and Human Retroviruses
Publisher
Mary Ann Liebert
Publication Date
Mar 01, 2021
Volume
37
Issue
3
Pages
224–232
Identifiers
DOI: 10.1089/AID.2020.0176
PMID: 33059459
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Despite the advent of antiretroviral therapy, people living with HIV suffer from a range of infectious and noninfectious pulmonary complications. HIV impairs antioxidant defenses and innate immune function of the alveolar macrophage by diminishing granulocyte macrophage-colony stimulating factor (GM-CSF) signaling. Since GM-CSF may be linked to mitochondria, we sought to determine the effects of HIV on GM-CSF receptor expression and alveolar macrophage mitochondrial function. At an academic medical center, studies were completed on alveolar macrophages isolated from both wild-type and HIV transgenic (HIV Tg) rats and human subjects with and without HIV. Primary macrophages were plated and evaluated for expression of GM-CSF receptor beta, phagocytic index, and mitochondrial function in the presence and absence of GM-CSF treatment. GM-CSF receptor expression and mitochondrial function were impaired in macrophages isolated from HIV Tg rats, and treatment with GM-CSF restored GM-CSF receptor expression and mitochondrial function. GM-CSF treatment of HIV Tg rats also increased alveolar macrophage levels of the mitochondrial proteins voltage-dependent anion-selective channel 1 (VDAC) and glucose-regulated protein 75 (Grp75). Similar to the HIV Tg rat model, impairments in mitochondrial bioenergetics were confirmed in alveolar macrophages isolated from human subjects with HIV. HIV-associated impairments in alveolar macrophage mitochondrial bioenergetics likely contribute to innate immune dysfunction in HIV infection, and GM-CSF treatment may offer a novel therapeutic strategy for mitigating these deleterious effects.

Report this publication

Statistics

Seen <100 times