ArticleThe Journal of clinical investigation2014
Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
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- Neutrophil CRACR2A Promotes Neutrophil Recruitment in Sterile Inflammation and Ischemic Stroke.Circulation · 2025Article
- trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing.Immunity · 2024Article
- Cargo-free particles divert neutrophil-platelet aggregates to reduce thromboinflammation.Nature communications · 2023Article
- FXII and sickle cell: the clot thickens.Blood · 2023Article
- Neutrophil DREAM promotes neutrophil recruitment in vascular inflammation.The Journal of experimental medicine · 2022Article
- The Role of Oxidative Stress in Acute Ischemic Stroke-Related Thrombosis.Oxidative medicine and cellular longevity · 2022Review
- The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside.Frontiers in oncology · 2022Review
- Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress.Frontiers in pharmacology · 2022Article
- ERO1-PDI Redox Signaling in Health and Disease.Antioxidants & redox signaling · 2021Review
- Microvascular thrombosis: experimental and clinical implications.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Repurposing pyridoxamine for therapeutic intervention of intravascular cell-cell interactions in mouse models of sickle cell disease.Haematologica · 2020Article
- Innate immune cells, major protagonists of sickle cell disease pathophysiology.Haematologica · 2020Review
- The dual role of platelet-innate immune cell interactions in thrombo-inflammation.Research and practice in thrombosis and haemostasis · 2020Review
- Neutrophil extracellular traps in breast cancer and beyond: current perspectives on NET stimuli, thrombosis and metastasis, and clinical utility for diagnosis and treatment.Breast cancer research : BCR · 2019Review
- Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in macrophages.Innate immunity · 2019Article
- Platelet Protein Disulfide Isomerase Promotes Glycoprotein Ibα-Mediated Platelet-Neutrophil Interactions Under Thromboinflammatory Conditions.Circulation · 2019Article
- Therapeutic strategies for sickle cell disease: towards a multi-agent approach.Nature reviews. Drug discovery · 2019Review
- Pathophysiology of Sickle Cell Disease.Annual review of pathology · 2019Review
- Factor XII in inflammation and wound healing.Current opinion in hematology · 2018Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Interactions between platelets, leukocytes, and activated endothelial cells are important during microvascular occlusion; however, the regulatory mechanisms of these heterotypic cell-cell interactions remain unclear. Here, using intravital microscopy to evaluate mice lacking specific isoforms of the serine/threonine kinase AKT and bone marrow chimeras, we found that hematopoietic cell-associated AKT2 is important for neutrophil adhesion and crawling and neutrophil-platelet interactions on activated endothelial cells during TNF-α-induced venular inflammation. Studies with an AKT2-specific inhibitor and cells isolated from WT and Akt KO mice revealed that platelet- and neutrophil-associated AKT2 regulates heterotypic neutrophil-platelet aggregation under shear conditions. In particular, neutrophil AKT2 was critical for membrane translocation of αMβ2 integrin, β2-talin1 interaction, and intracellular Ca2+ mobilization. We found that the basal phosphorylation levels of AKT isoforms were markedly increased in neutrophils and platelets isolated from patients with sickle cell disease (SCD), an inherited hematological disorder associated with vascular inflammation and occlusion. AKT2 inhibition reduced heterotypic aggregation of neutrophils and platelets isolated from SCD patients and diminished neutrophil adhesion and neutrophil-platelet aggregation in SCD mice, thereby improving blood flow rates. Our results provide evidence that neutrophil AKT2 regulates αMβ2 integrin function and suggest that AKT2 is important for neutrophil recruitment and neutrophil-platelet interactions under thromboinflammatory conditions such as SCD.
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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.