ArticleAnesthesiology2010
Sevoflurane binds and allosterically blocks integrin lymphocyte function-associated antigen-1.
Article in Anesthesiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
- Review
- Mechanism of isoflurane‑mediated breast cancer growthOncology letters · 2024Article
- Molecular Aspects of Volatile Anesthetic-Induced Organ Protection and Its Potential in Kidney Transplantation.International journal of molecular sciences · 2021Review
- Mechanistic consideration of the effect of perioperative volatile anesthetics on phagocytes.Clinical immunology (Orlando, Fla.) · 2021Review
- Surgical Site Infections and Perioperative Optimization of Host Immunity by Selection of Anesthetics.BioMed research international · 2021Review
- The Role of General Anesthetic Drug Selection in Cancer Outcome.BioMed research international · 2021Review
- The effect of anesthetics on toll like receptor 9.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Distant survival for patients undergoing surgery using volatile versus IV anesthesia for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study.BMC anesthesiology · 2020Article
- Article
- Volatile anesthetics isoflurane and sevoflurane directly target and attenuate Toll-like receptor 4 system.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The volatile anesthetic sevoflurane reduces neutrophil apoptosisFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Effects of propofol-based total intravenous anesthesia on gastric cancer: a retrospective study.OncoTargets and therapy · 2018Article
- From the Cover: Prolonged Exposure to Volatile Anesthetic Isoflurane Worsens the Outcome of Polymicrobial Abdominal Sepsis.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- The effect of different anesthetics on tumor cytotoxicity by natural killer cells.Toxicology letters · 2017Article
- Anaesthetic challenges in cancer patients: current therapies and pain management.Acta medica Lituanic · 2017Article
- Mechanisms of the Immunological Effects of Volatile Anesthetics: A Review.Anesthesia and analgesia · 2016Review
- Immune Modulation by Volatile Anesthetics.Anesthesiology · 2016Review
- Differential effects of volatile anesthetics on leukocyte integrin macrophage-1 antigen.Journal of immunotoxicology · 2016Article
- Exposure to general anesthesia and the risk of dementia.Journal of pain research · 2015Review
- Sepsis pathophysiology and anesthetic consideration.Cardiovascular & hematological disorders drug targets · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundVolatile anesthetics have been shown to modify immune cell functions via several mechanisms, some of which have been only partially elucidated. We demonstrated that isoflurane inhibits primary leukocyte integrin lymphocyte function-associated antigen-1 (LFA-1) by binding to the allosteric cavity critical for conformational activation to its high-affinity form. It remains to be determined whether the allosteric inhibition of LFA-1 by isoflurane can be generalized to other anesthetics such as sevoflurane.
methodsThe effects of sevoflurane on the ability of LFA-1 to bind to its counter-ligand, intercellular adhesion molecule-1, was studied in leukocytes by flow cytometry. To examine whether sevoflurane acts directly on LFA-1, we measured ligand-binding using beads coated with purified LFA-1 protein. To distinguish between competitive versus allosteric inhibition, we analyzed the effects of sevoflurane on both wild-type and mutant-locked high-affinity LFA-1. One-way analysis of variance was employed for statistical analysis of the data. Nuclear magnetic resonance spectroscopy was used to identify sevoflurane binding site(s).
resultsSevoflurane at clinically relevant concentrations inhibited the ligand-binding function of LFA-1 in leukocytes as well as in cell-free assays (P<0.05). Sevoflurane blocked wild-type but not locked high-affinity LFA-1, thereby demonstrating an allosteric mode of inhibition. Nuclear magnetic resonance spectroscopy revealed that sevoflurane bound to the allosteric cavity, to which LFA-1 allosteric antagonists and isoflurane also bind.
conclusionsThis study suggests that sevoflurane also blocks the activation-dependent conformational changes of LFA-1 to the high-affinity form. The allosteric mode of action exemplified by sevoflurane and isoflurane via LFA-1 might represent one of the underlying mechanisms of anesthetic-mediated immunomodulation.
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