Activation of Ca2+-activated potassium channels is involved in lysophosphatidylcholine-induced monocyte adhesion to endothelial cells

ObjectiveCa2+-activated K+-channels (BKCa) play an important role in lysophosphatidylcholine (LPC)-induced endothelial dysfunction. Aim of our study was to investigate whether LPC-induced activation of BKCa is also involved in monocyte adhesion to endothelial cells (EC).Methods and resultsMeasurement of membrane potential (MP) was performed using the fluorescence dye DiBAC. Adhesion of the monocytotic cell line U937 to EC was analysed by 3[H]-thymidine-adhesion-assay. Expression of ICAM-1 and VCAM-1 were analyzed by FACS. LPC induced a hyperpolarization of EC in a dose-dependent manner with the maximum seen with 2 μM. This was prevented by the BKCa-inhibitor iberiotoxin (IBX, 100 nM). Adhesion of U937 cells to EC was increased after stimulation of EC with LPC. This effect was time-dependent with the maximum seen after 4 h. LPC-induced adhesion was significantly reduced when EC were co-incubated with IBX, or NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI, 5 μM) and also blocked by addition of 2-aminoethoxydiphenylborate (2-APB, 100 μM) or the calcium-chelator BAPTA (10 μM). Stimulation of U937 cells with LPC did not result in an increased adhesion to unstimulated EC.ConclusionActivation of the endothelial BKCa plays an important role in monocyte adhesion to endothelial cells.