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

The held of research considering the working mechanism of anesthetic agents is a complex one and the site or sites of action of general anesthetics ar e yet to he elucidated. Through the years, on the molecular level, the disc ussion has shifted from the lipid theories to the more specific interaction with the proteins responsible for the signal transduction. While this appr oach led to several models, they offer, at best, partial explanations for t he observed phenomena, Anesthetic agents interact with many systems, of whi ch the neuronal is best studied. leaving interaction with the immune defens e system relatively unexplored. In this study we focus on the interaction o f ethanol and halothane with the co-localization on the membrane of HLA I a nd II molecules. We show that ethanol tends to randomize the distribution o f 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-localizat ion of molecules that may form a functional network. The relevance of this finding depends on the importance of these networks for extracellular and i ntracellular processes. (C) 2000 Elsevier Science S.A. All rights reserved.