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ANESTHETIC PHARMACOLOGY

The Effect of Isoflurane on Neutrophil Selectin and ß₂-Integrin Activation In Vitro

Lothar W. de Rossi, MD^*, Nicola A. Horn, MD^*, Wolfgang Buhre, MD^*, Florian Gass, Gabriele Hutschenreuter, MD, and Rolf Rossaint, MD^*

*Department of Anesthesiology and Institute of Transfusion Medicine, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany

Address correspondence and reprint requests to Lothar W. de Rossi, MD, Department of Anesthesiology, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany. Address e-mail to L.derossi{at}gmx.de

Isoflurane is reported to reduce ischemia-reperfusion injury. Lower expression of CD11b may be responsible for attenuated postischemic neutrophil adhesion to vascular endothelium. However, neutrophil adhesion to vascular endothelium is a multistep process involving several selectins and ß₂-integrins. Therefore, we assessed whether isoflurane affects the activation of the selectins P-selectin glycoprotein ligand-1 (PSGL-1) and L-selectin and the ß₂-integrins CD11a and CD11b. Whole blood was incubated for 60 min with 0.5 or 1 minimum alveolar anesthetic concentration (MAC) isoflurane. After incubation, neutrophils were activated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol-12-myristate-13-acetate (PMA). Activation of adhesion molecules was evaluated via flow cytometry, and 1 MAC isoflurane reduced the expression of CD11a in the unstimulated samples. After stimulation with FMLP and PMA, shedding of L-selectin was lower in the presence of isoflurane. Furthermore, 1 MAC isoflurane reduced FMLP-induced activation of CD11a and CD11b compared with unexposed blood samples. These results demonstrate that isoflurane affects the activation of three adhesion molecules involved in the multistep process of neutrophil recruitment. First, isoflurane inhibits the activation of L-selectin, which mediates the neutrophil tethering and rolling on the vascular endothelium. Second, isoflurane attenuates the activation of both ß₂-integrins—CD11a and CD11b—which mediate firm adhesion and transendothelial migration.

IMPLICATIONS: Adhesion of neutrophils to endothelial cells in reperfusion injury is mediated by different adhesion molecules. This study indicates that the inhibiting effect of isoflurane on neutrophil recruitment may be mediated by a decreased activation of the L-selectin and by attenuation of the activation of the ß₂-integrins CD11a and CD11b.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999