ArticleProceedings of the National Academy of Sciences of the United States of America2001
Genetically engineered macrophages expressing IFN-gamma restore alveolar immune function in scid mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Designing Chimeric Antigen Receptors for Myeloid Immune Cells.Journal of cancer biology & research · 2024Article
- Harnessing bioengineered myeloid progenitors for precision immunotherapies.NPJ Regenerative medicine · 2023Review
- Therapeutic utility of engineered myeloid cells in the tumor microenvironment.Cancer gene therapy · 2023Review
- Potential therapeutic targets of macrophages in inhibiting immune damage and fibrotic processes in musculoskeletal diseases.Frontiers in immunology · 2023Review
- IL-6-elafin genetically modified macrophages as a lung immunotherapeutic strategy against Pseudomonas aeruginosa infections.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Tailoring Materials for Modulation of Macrophage Fate.Advanced materials (Deerfield Beach, Fla.) · 2021Review
- Effect of the cagW-based gene vaccine on the immunologic properties of BALB/c mouse: an efficient candidate for Helicobacter pylori DNA vaccine.Journal of nanobiotechnology · 2020Article
- MEG3-4 is a miRNA decoy that regulates IL-1β abundance to initiate and then limit inflammation to prevent sepsis during lung infection.Science signaling · 2018Article
- Chitosan-DNA nanoparticles enhanced the immunogenicity of multivalent DNA vaccination on mice against Trueperella pyogenes infection.Journal of nanobiotechnology · 2018Article
- Atg7 Deficiency Intensifies Inflammasome Activation and Pyroptosis inJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- DNA Repair Interacts with Autophagy To Regulate Inflammatory Responses to Pulmonary Hyperoxia.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Airway delivery of interferon-γ overexpressing macrophages confers resistance to Mycobacterium avium infection in SCID mice.Physiological reports · 2016Article
- Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.PLoS biology · 2016Article
- Engineering macrophages to control the inflammatory response and angiogenesis.Experimental cell research · 2015Article
- Inhibition of p-IκBα Ubiquitylation by Autophagy-Related Gene 7 to Regulate Inflammatory Responses to Bacterial Infection.The Journal of infectious diseases · 2015Article
- Atg7 enhances host defense against infection via downregulation of superoxide but upregulation of nitric oxide.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Pulmonary macrophage transplantation therapy.Nature · 2014Article
- Atg7 deficiency impairs host defense against Klebsiella pneumoniae by impacting bacterial clearance, survival and inflammatory responses in mice.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Reversal of immunodeficiency in the lung by gene therapy is limited in part by the difficulty of transfecting lung cells in vivo. Many options exist for successfully transfecting cells in vitro, but they are not easily adapted to the in vivo condition. To overcome this limitation, we transduced macrophages in vitro with the murine IFN-gamma (mIFN-gamma) gene and intratracheally delivered the macrophages to express mIFN-gamma in vivo. A recombinant retroviral vector pSF91 system was modified to encode mIFN-gamma and enhanced green fluorescent protein (EGFP). A murine macrophage cell line J774A.1 transduced with the retroviral supernatant increased secretion from undetectable levels to 131.6 +/- 4.2 microg/ml mIFN-gamma at 24 h in vitro. The mIFN-gamma-producing macrophages were intratracheally instilled into mechanically ventilated scid mice. mIFN-gamma levels in the bronchoalveolar lavage increased from undetectable levels at baseline to 158.8 +/- 5.1 pg/ml at 48 h (P < 0.001). Analysis of the lavaged cells for EGFP expression revealed that EGFP expression was directly proportional to the number of transduced macrophages instilled into the lung. Immune function was partially restored in the alveolar spaces of scid mice with evidence of enhanced MHC class II antigen expression and increased phagocytosis (P < 0.05). Tumor necrosis factor alpha was increased from undetectable at baseline to 103.5 +/- 11.4 pg/ml. In contrast, i.p. administration of the engineered macrophages did not enhance IFN-gamma levels in the lung. Our study suggests airway delivery of genetically engineered macrophages expressing mIFN-gamma gene can partially restore significant immune activity in the lungs of immunodeficient mice.
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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.