In vitro studies on immunosuppression with verapamil
Hailer, N.P.; Blaheta, R.A.; Harder, S.; Scholz, M.; Encke, A.; Markus, B.H.
Zentralblatt für Chirurgie 119(5): 347-354
1994
ISSN/ISBN: 0044-409X PMID: 8023602 Document Number: 432552
AIMS OF THE INVESTIGATION: It is known that Verapamil and other calcium channel blockers possess immunosuppressive properties. It has been suggested that they exert their effects by antagonising protein kinase C (PKC) or calmodulin. Our aim was to investigate whether the adhesion of lymphocytes to allogenic endothelial cells and lymphocyte migration are impaired in the presence of Verapamil. The role of PKC and calmodulin during expression of adhesion molecules, the expression of adhesion molecules under the influence of Verapamil and lymphocyte motility on endothelial cell monolayers were investigated. Human endothelial cells (EC) were obtained from umbilical chord veins and incubated as dissociate primary cultures. Expression of adhesion molecules on EC was determined by quantitative immunofluorescence using the CytoFluor 2300-system. Studies on lymphocyte motility were performed by phase contrast microscopy using video scope analysis. Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule (VCAM-1) and Endothelial Leukocyte Adhesion Molecule I (ELAM-1) was dose-dependently reduced by the application of PKC-inhibitor H7. Expression of ICAM-1 and VCAM-1 was also inhibited by the calmodulin-antagonist W7. Surprisingly, neither R- nor S-Verapamil inhibited adhesion molecule expression, we even observed significant enhancement of ELAM-1- and ICAM-1-expression. Nevertheless, lymphocyte motility on allogenic EC monolayers was impaired in the presence of R-verapamil, the enantiomer that is inactive as a calcium channel blocker. Verapamil reduces lymphocyte motility and is therefore effective in impairing lymphocyte-endothelial cell-interactions. These effects seem to be independent of calcium channel blockade and are probably not due to inhibition of PKC or calmodulin.