ArticleThe Journal of biological chemistry2014
γ-Interferon-inducible lysosomal thiol reductase (GILT) maintains phagosomal proteolysis in alternatively activated macrophages.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 71 citations in OpenAlex.
- Review
- Lysosome as a Chemical Reactor.International journal of molecular sciences · 2025Review
- Article
- Approaches to Measuring Reductive and Oxidative Events in Phagosomes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Label-Free Quantitative Proteomics to Explore the Action Mechanism of the Pharmaceutical-GradeMolecules (Basel, Switzerland) · 2022Article
- Ifi30 Is Required for Sprouting Angiogenesis During Caudal Vein Plexus Formation in Zebrafish.Frontiers in physiology · 2022Article
- Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes.Nature communications · 2021Article
- A non-immunological role for γ-interferon-inducible lysosomal thiol reductase (GILT) in osteoclastic bone resorption.Science advances · 2021Article
- A physiologic overview of the organ-specific transcriptome of the cattle tick Rhipicephalus microplus.Scientific reports · 2020Article
- Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics.Respiratory research · 2020Review
- Lysosomal peptidases in innate immune cells: implications for cancer immunity.Cancer immunology, immunotherapy : CII · 2020Review
- Growth hormone-mediated reprogramming of macrophage transcriptome and effector functions.Scientific reports · 2019Article
- Biguanide is a modifiable pharmacophore for recruitment of endogenous ZnBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Review
- A lysosome-targetable fluorescent probe for the simultaneous sensing of Cys/Hcy and GSH from different emission channels.RSC advances · 2019Article
- Lysosome-Targeted Single Fluorescence Probe for Two-Channel Imaging Intracellular SO₂ and Biothiols.Molecules (Basel, Switzerland) · 2019Article
- Cysteine Cathepsins in Tumor-Associated Immune Cells.Frontiers in immunology · 2019Review
- Microglia express gamma-interferon-inducible lysosomal thiol reductase in the brains of Alzheimer's disease and Nasu-Hakola disease.Intractable & rare diseases research · 2018Article
- Measuring Phagosome pH by Ratiometric Fluorescence Microscopy.Journal of visualized experiments : JoVE · 2015Article
- Diverse cellular and organismal functions of the lysosomal thiol reductase GILT.Molecular immunology · 2015Review
- Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis.PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although it is known that lysosomal cysteine cathepsins require a reducing environment for optimal activity, it is not firmly established how these enzymes are maintained in their reduced-active state in the acidic and occasionally oxidative environment within phagosomes and lysosomes. γ-Interferon-inducible lysosomal thiol reductase (GILT) has been the only enzyme described in the endosomes, lysosomes, and phagosomes with the potential to catalyze the reduction of cysteine cathepsins. Our goal in the current study was to assess the effect of GILT on major phagosomal functions with an emphasis on proteolytic efficiency in murine bone marrow-derived macrophages. Assessment of phagosomal disulfide reduction upon internalization of IgG-opsonized experimental particles confirmed a major role for GILT in phagosomal disulfide reduction in both resting and interferon-γ-activated macrophages. Furthermore we observed a decrease in early phagosomal proteolytic efficiency in GILT-deficient macrophages, specifically in the absence of an NADPH oxidase-mediated respiratory burst. This deficiency was more prominent in IL-4-activated macrophages that inherently possess lower levels of NADPH oxidase activity. Finally, we provide evidence that GILT is required for optimal activity of the lysosomal cysteine protease, cathepsin S. In summary, our results suggest a role for GILT in maintaining cysteine cathepsin proteolytic efficiency in phagosomes, particularly in the absence of high NADPH oxidase activity, which is characteristic of alternatively activated macrophages.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.