ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Arginase I release from activated neutrophils induces peripheral immunosuppression in a murine model of stroke.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Immunomodulation for stroke-associated pneumonia: a systematic review of mechanistic insight and emerging therapeutic strategies in animal models.Frontiers in immunology · 2026Pooled it
- S100A8/A9 Inhibition Reduces Neutrophil Extracellular Trap Formation and Mitigates Sepsis-Related Liver Injury.Journal of inflammation research · 2026Article
- Article
- Neutrophil Heterogeneity and its Roles in the Inflammatory Network after Ischemic Stroke.Current neuropharmacology · 2023Article
- Depletion of Arg1-Positive Microglia/Macrophages Exacerbates Cerebral Ischemic Damage by Facilitating the Inflammatory Response.International journal of molecular sciences · 2022Article
- Systemic inflammation after stroke: implications for post-stroke comorbidities.EMBO molecular medicine · 2022Review
- Brain-associated innate leukocytes display diverse inflammatory states following experimental stroke.Immunology and cell biology · 2022Article
- Neutrophils inhibit CD8World journal of emergency medicine · 2022Article
- Neutrophil-specific deletion of Syk results in recruitment-independent stabilization of the barrier and a long-term improvement in cognitive function after traumatic injury to the developing brain.Neurobiology of disease · 2021Article
- Stroke-induced immunosuppression: implications for the prevention and prediction of post-stroke infections.Journal of neuroinflammation · 2021Review
- Innate Signaling in the CNS Prevents Demyelination in a Focal EAE Model.Frontiers in neuroscience · 2021Article
- Improved mouse models and advanced genetic and genomic technologies for the study of neutrophils.Drug discovery today · 2020Review
- Early elevated neutrophil-to-lymphocyte ratio associated with remote diffusion-weighted imaging lesions in acute intracerebral hemorrhage.CNS neuroscience & therapeutics · 2020Article
- Arginase Pathway in Acute Retina and Brain Injury: Therapeutic Opportunities and Unexplored Avenues.Frontiers in pharmacology · 2020Review
- Distinct Neutrophil Populations in the Spleen During PICS.Frontiers in immunology · 2020Article
- Myeloid Cell-Derived Arginase in Cancer Immune Response.Frontiers in immunology · 2020Review
- Alteration of microRNA 340-5p and Arginase-1 Expression in Peripheral Blood Cells during Acute Ischemic Stroke.Molecular neurobiology · 2019Article
- The spleen may be an important target of stem cell therapy for stroke.Journal of neuroinflammation · 2019Review
- Orchestration of Adaptive T Cell Responses by Neutrophil Granule Contents.Mediators of inflammation · 2019Review
- The Diverse Biological Functions of Neutrophils, Beyond the Defense Against Infections.Inflammation · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Transient suppression of peripheral immunity is a major source of complication for patients suffering from ischemic stroke. The release of Arginase I (ArgI) from activated neutrophils has recently been associated with T-cell dysfunction in a number of pathologies. However, this pathway has not been previously explored in ischemic stroke. Using the murine model of transient middle cerebral artery occlusion, we explored effects of stroke on peripheral T-cell function and evaluated the role of neutrophils and ArgI. Stimulation of splenic T cells from post-stroke animals with anti-CD3/CD28 resulted in decreased proliferation and interferon-γ production when compared with sham-surgery controls. Flow cytometric analysis of intrasplenic leukocytes exposed the presence of a transient population of activated neutrophils that correlated quantitatively with elevated ArgI levels in culture media. In vitro activation of purified resting neutrophils from unmanipulated controls confirmed the capacity for murine neutrophils to release ArgI from preformed granules. We observed decreased expression of the L-arg-sensitive CD3ζ on T cells, consistent with decreased functional activity. Critically, L-arg supplementation restored the functional response of post-stroke T cells to mitogenic stimulation. Together, these data outline a novel mechanism of reversible, neutrophil-mediated peripheral immunosuppression related to ArgI release following ischemic stroke.
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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.