ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2017
Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia-reperfusion injury.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Red blood cells could protect miRNAs from degradation or loss thanks to Argonaute 2 binding.FEBS open bio · 2025Article
- Drug-loaded erythrocytes: Modern approaches for advanced drug delivery for clinical use.Heliyon · 2024Review
- Drug transport by red blood cells.Frontiers in physiology · 2023Review
- Red Blood Cell Hitchhiking: A Novel Approach for Vascular Delivery of Nanocarriers.Annual review of biomedical engineering · 2021Article
- Article
- Fibrin-modulating nanogels for treatment of disseminated intravascular coagulation.Blood advances · 2021Article
- Vascular Drug Delivery Using Carrier Red Blood Cells: Focus on RBC Surface Loading and Pharmacokinetics.Pharmaceutics · 2020Review
- Recombinant human thrombomodulin attenuated sepsis severity in a non-surgical preterm mouse model.Scientific reports · 2020Article
- Novel Fast and Reliable Method for Nano-Erythrosome Production Using Shear Force.Drug design, development and therapy · 2020Article
- Reactive species-induced microvascular dysfunction in ischemia/reperfusion.Free radical biology & medicine · 2019Review
- Biocompatible coupling of therapeutic fusion proteins to human erythrocytes.Blood advances · 2018Article
- ICAM-1-targeted thrombomodulin mitigates tissue factor-driven inflammatory thrombosis in a human endothelialized microfluidic model.Blood advances · 2017Article
- Impact of thrombosis on pulmonary endothelial injury and repair following sepsis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
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Authors and funding
11 authors.
Funding
Abstract
Endothelial thrombomodulin (TM) regulates coagulation and inflammation via several mechanisms, including production of activated protein C (APC). Recombinant APC and soluble fragments of TM (sTM) have been tested in settings associated with insufficiency of the endogenous TM/APC pathway, such as sepsis. We previously designed a fusion protein of TM [single-chain variable fragment antibody (scFv)/TM] targeted to red blood cells (RBCs) to improve pharmacokinetics and antithrombotic effects without increasing bleeding. Here, scFv/TM was studied in mouse models of systemic inflammation and ischemia-reperfusion injury. Injected concomitantly with or before endotoxin, scFv/TM provided more potent protection against liver injury and release of pathological mediators than sTM, showing similar efficacy at up to 50-fold lower doses. scFv/TM provided protection when injected after endotoxin, whereas sTM did not, and augmented APC production by thrombin ∼50-fold more than sTM. However, scFv/TM injected after endotoxin did not reduce thrombin/antithrombin complexes; nor did antibodies that block APC anticoagulant activity suppress the prophylactic anti-inflammatory effect of scFv/TM. Therefore, similar to endogenous TM, RBC-anchored scFv/TM activates several protective pathways. Finally, scFv/TM was more effective at reducing cerebral infarct volume and alleviated neurological deficits than sTM after cerebral ischemia/reperfusion injury. These results indicate that RBC-targeted scFv/TM exerts multifaceted cytoprotective effects and may find utility in systemic and focal inflammatory and ischemic disorders.-Carnemolla, R., Villa, C. H., Greineder, C. F., Zaitseva, S., Patel, K. R., Kowalska, M. A., Atochin, D. N., Cines, D. B., Siegel, D. L., Esmon, C. T., Muzykantov, V. R. Targeting thrombomodulin to circulating red blood cells augments its protective effects in models of endotoxemia and ischemia-reperfusion injury.
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