Activation of Ca2+ -activated potassium channels is involved in lysophosphatidylcholine-induced monocyte adhesion to endothelial cells.
OBJECTIVE
Ca(2+)-activated K(+)-channels (BK(Ca)) play an important role in lysophosphatidylcholine (LPC)-induced endothelial dysfunction. Aim of our study was to investigate whether LPC-induced activation of BK(Ca) is also involved in monocyte adhesion to endothelial cells (EC).


RESULTS
Measurement 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 microM. This was prevented by the BK(Ca)-inhibitor iberiotoxin (IBX, 100nM). Adhesion of U937 cells to EC was increased after stimulation of EC with LPC. This effect was time-dependent with the maximum seen after 4h. LPC-induced adhesion was significantly reduced when EC were co-incubated with IBX, or NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI, 5 microM) and also blocked by addition of 2-aminoethoxydiphenylborate (2-APB, 100 microM) or the calcium-chelator BAPTA (10 microM). Stimulation of U937 cells with LPC did not result in an increased adhesion to unstimulated EC.


CONCLUSIONS
Activation of the endothelial BK(Ca) plays an important role in monocyte adhesion to endothelial cells.
Erdogan
Ali
A
Justus-Liebig-University of Giessen, Department of Cardiology and Angiology, Giessen, Germany.
Schaefer
Martina Barbara
MB
Kuhlmann
Christoph Ruediger Wolfram
CR
Most
Astrid
A
Hartmann
Marc
M
Mayer
Konstantin
K
Renner
Fabrice Christoph
FC
Schaefer
Claudia
C
Abdallah
Yaser
Y
Hoelschermann
Hans
H
Schaefer
Christian Alexander
CA
D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism
D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008244:Lysophosphatidylcholines; D009861:Onium Compounds; D010455:Peptides; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; C064719:iberiotoxin; D019255:NADPH Oxidases; D002118:Calcium