The volatile anesthetic isoflurane perturbs conformational activation of integrin LFA-1 by binding to the allosteric regulatory cavity.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Koichi YukiMotomu Shimaoka

Abstract

The molecular and structural basis of anesthetic interactions with conformations and functionalities of cell surface receptors remains to be elucidated. We have demonstrated that the widely used volatile anesthetic isoflurane blocks the activation-dependent conformational conversion of integrin lymphocyte function associated antigen-1 (LFA-1), the major leukocyte cell adhesion molecule, to a high-affinity configuration. Perturbation of LFA-1 activation by isoflurane at clinically relevant concentrations leads to the inhibition of T-cell interactions with target cells as well as ligand-triggered intracellular signaling. Nuclear magnetic resonance spectroscopy reveals that isoflurane binds within a cavity in the LFA-1 ligand-binding domain, which is a previously identified drug-binding site for allosteric small-molecule antagonists that stabilize LFA-1 in a low-affinity conformation. These results provide a potential mechanism for the immunomodulatory properties of isoflurane.

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Citations

Oct 26, 2012·Journal of Anesthesia·Carla CarboMotomu Shimaoka
Oct 5, 2010·Nature Reviews. Drug Discovery·Dermot CoxNiamh Moran
Apr 1, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hongmin ZhangMotomu Shimaoka
Jul 21, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Koichi YukiRoderic G Eckenhoff
Mar 10, 2011·Anesthesia and Analgesia·Koichi YukiMotomu Shimaoka
Feb 25, 2014·Current Anesthesiology Reports·Brian P WeiserRoderic G Eckenhoff
Jun 26, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Roderic G Eckenhoff, Krzysztof F Laudansky
Apr 14, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K A LandskronerA Treiber
Mar 10, 2015·Journal of Immunotoxicology·Sungeun Jung, Koichi Yuki
Mar 23, 2015·Veterinary Immunology and Immunopathology·Grégory MinguetCharlotte Sandersen
Mar 30, 2018·Anesthesia and Analgesia·Julie A FischerMisha Perouansky
Jan 30, 2014·Perioperative Medicine·Daniela C IonescuDaniel I Sessler
May 10, 2019·PloS One·Hui ZhaKoichi Yuki
Oct 21, 2016·Anesthesia and Analgesia·Kellie A WollRoderic G Eckenhoff
Jun 17, 2016·Anesthesia and Analgesia·Koichi Yuki, Roderic G Eckenhoff
Sep 13, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sophia KoutsogiannakiKoichi Yuki
Nov 2, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Toshiaki OkunoKoichi Yuki
Mar 10, 2020·Anesthesia and Analgesia·Yusuke MitsuiKoichi Yuki
Sep 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sophia KoutsogiannakiKoichi Yuki
Nov 21, 2020·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Koichi YukiSulpicio G Soriano
Mar 26, 2021·BioMed Research International·Koichi Yuki, Miho Shibamura-Fujiogi
Apr 4, 2021·International Journal of Molecular Sciences·Gertrude J Nieuwenhuijs-MoekeHenri G D Leuvenink
Mar 17, 2010·ACS Chemical Neuroscience·Roderic G EckenhoffWilliam P Dailey
Oct 17, 2021·Fundamental & Clinical Pharmacology·Priyanka SahaDona Sinha

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