title: Ethanol and halothane differently modulate HLA class I and class II oligomerization. A new look at the mode of action of anesthetic agents through fluorescence spectroscopy.
abstract: The field of research considering the working mechanism of anesthetic agents is a complex one and the site or sites of action of general anesthetics are yet to be elucidated. Through the years, on the molecular level, the discussion has shifted from the lipid theories to the more specific interaction with the proteins responsible for the signal transduction. While this approach led to several models, they offer, at best, partial explanations for the observed phenomena. Anesthetic agents interact with many systems, of which the neuronal is best studied, leaving interaction with the immune defense system relatively unexplored. In this study we focus on the interaction of ethanol and halothane with the co-localization on the membrane of HLA I and II molecules. We show that ethanol tends to randomize the distribution of HLA I and II molecules, while halothane increases the clustering of HLA I proteins. The notion that anesthetics modulate cell function by disrupting clustering and thereby promoting a random distribution is a novel approach that may explain the general involvement of many systems during exposition to anesthetic drugs. In this study we show the disturbance of co-localization of molecules that may form a functional network. The relevance of this finding depends on the importance of these networks for extracellular and intracellular processes.
authors.affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Dzoljic
authors.forename: L
authors.initials: L
authors.lastname: Bene
authors.forename: Z
authors.initials: Z
authors.lastname: Krasznai
authors.forename: S
authors.initials: S
authors.lastname: Damjanovich
authors.forename: B
authors.initials: B
authors.lastname: Van Duijn
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes; D002460:Cell Line; D004735:Energy Transfer; D000431:Ethanol / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D046911:Macromolecular Substances; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D018685:Anesthetics, Inhalation; D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D000431:Ethanol; D006221:Halothane