Differential effects of volatile anesthetics on leukocyte integrin macrophage-1 antigen

Journal of Immunotoxicology
Sungeun Jung, Koichi Yuki

Abstract

Macrophage-1 antigen (Mac-1, αMβ2) is a leukocyte adhesion molecule that plays a significant role in leukocyte crawling and phagocytosis, and is homologous to its sister protein leukocyte function-associated antigen-1 (LFA-1, αLβ2). The authors have previously demonstrated that volatile anesthetics isoflurane and sevoflurane bound to and inhibited LFA-1. Here, the hypothesis tested was that isoflurane and sevoflurane would inhibit Mac-1. A binding assay of Mac-1 to its ligand inter-cellular adhesion molecule-1 (ICAM-1) using V-bottom plates was established. The effect of isoflurane and sevoflurane on Mac-1 was examined using this ICAM-1 binding assay and by probing exposure of activation-sensitive epitopes. The docking program Glide was used to predict anesthetic binding site(s) on Mac-1. The functional role of this predicted binding site was then assessed by introducing point mutations in this region. Lastly, the effect of anesthetic on activating mutants was evaluated. The results indicated that isoflurane inhibited binding of Mac-1 to ICAM-1, but sevoflurane did not. Isoflurane also attenuated the exposure of the activation-sensitive epitopes. The docking simulation predicted the isoflurane binding site to be at the cavity u...Continue Reading

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Citations

May 10, 2019·PloS One·Hui ZhaKoichi Yuki
Jun 11, 2016·Anesthesiology·Lindsay M StollingsYan Xu
Sep 13, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sophia KoutsogiannakiKoichi Yuki
Mar 10, 2020·Anesthesia and Analgesia·Yusuke MitsuiKoichi Yuki
Feb 26, 2020·International Journal of Molecular Sciences·Monika BednarczykMatthias Bros
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
May 27, 2021·BioMed Research International·Koichi YukiSophia Koutsogiannaki
Jul 28, 2021·Cancer Immunology, Immunotherapy : CII·Houshi XuMeiqing Lou

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