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Antithrombin and Its Role in Host Defense and Inflammation.
Schlömmer, Christine; Brandtner, Anna; Bachler, Mirjam.
  • Schlömmer C; Department of Cardiac Thoracic Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria.
  • Brandtner A; Division of General and Surgical Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
  • Bachler M; Division of General and Surgical Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Int J Mol Sci ; 22(8)2021 Apr 20.
Article in English | MEDLINE | ID: covidwho-1299445
ABSTRACT
Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin. However, AT levels drop in systemic inflammatory diseases. The reason for this decline is consumption by the coagulation system but also by immunological processes. Aside from the primarily known anticoagulant effects, AT elicits distinct anti-inflammatory signaling responses. It binds to structures of the glycocalyx (syndecan-4) and further modulates the inflammatory response of endothelial cells and leukocytes by interacting with surface receptors. Additionally, AT exerts direct antimicrobial effects depending on AT glycosylation it can bind to and perforate bacterial cell walls. Peptide fragments derived from proteolytic degradation of AT exert antibacterial properties. Despite these promising characteristics, therapeutic supplementation in inflammatory conditions has not proven to be effective in randomized control trials. Nevertheless, new insights provided by subgroup analyses and retrospective trials suggest that a recommendation be made to identify the patient population that would benefit most from AT substitution. Recent experiment findings place the role of various AT isoforms in the spotlight. This review provides an overview of new insights into a supposedly well-known molecule.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antithrombins / Disease Susceptibility / Host-Pathogen Interactions / Disease Resistance / Inflammation Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22084283

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antithrombins / Disease Susceptibility / Host-Pathogen Interactions / Disease Resistance / Inflammation Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22084283