The effect of isoflurane on neutrophil selectin and beta(2)-integrin activation in vitro.
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 beta(2)-integrins. Therefore, we assessed whether isoflurane affects the activation of the selectins P-selectin glycoprotein ligand-1 (PSGL-1) and L-selectin and the beta(2)-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 beta(2)-integrins-CD11a and CD11b-which mediate firm adhesion and transendothelial migration.


CONCLUSIONS
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 beta(2)-integrins CD11a and CD11b.
Department of Anesthesiology, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany. L.derossi@gmx.de
Lothar W
LW
de Rossi
Nicola A
NA
Horn
Wolfgang
W
Buhre
Florian
F
Gass
Gabriele
G
Hutschenreuter
Rolf
R
Rossaint
D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D019041:L-Selectin / Q000096:biosynthesis*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007530:Isoflurane; D013755:Tetradecanoylphorbol Acetate