钙离子激活的钾通道的激活参与溶血磷脂酰胆碱诱导的单核细胞与内皮细胞的黏附。
Activation of Ca2+ -activated potassium channels is involved in lysophosphatidylcholine-induced monocyte adhesion to endothelial cells.
作者信息
Erdogan Ali, Schaefer Martina Barbara, Kuhlmann Christoph Ruediger Wolfram, Most Astrid, Hartmann Marc, Mayer Konstantin, Renner Fabrice Christoph, Schaefer Claudia, Abdallah Yaser, Hoelschermann Hans, Schaefer Christian Alexander
机构信息
Justus-Liebig-University of Giessen, Department of Cardiology and Angiology, Giessen, Germany.
出版信息
Atherosclerosis. 2007 Jan;190(1):100-5. doi: 10.1016/j.atherosclerosis.2006.02.035. Epub 2006 Apr 4.
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).
METHODS AND 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.
CONCLUSION
Activation of the endothelial BK(Ca) plays an important role in monocyte adhesion to endothelial cells.
目的
钙激活钾通道（BK(Ca)）在溶血磷脂酰胆碱（LPC）诱导的内皮功能障碍中起重要作用。本研究的目的是探讨LPC诱导的BK(Ca)激活是否也参与单核细胞与内皮细胞（EC）的黏附。
方法与结果
使用荧光染料DiBAC测量膜电位（MP）。通过[3H] - 胸苷黏附试验分析单核细胞系U937与EC的黏附。通过流式细胞术分析细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达。LPC以剂量依赖方式诱导EC超极化，2 microM时达到最大值。这被BK(Ca)抑制剂iberiotoxin（IBX，100 nM）阻断。用LPC刺激EC后，U937细胞与EC的黏附增加。这种效应具有时间依赖性，4小时后达到最大值。当EC与IBX或烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）氧化酶抑制剂二亚苯基碘鎓（DPI，5 microM）共同孵育时，LPC诱导的黏附显著降低，并且添加2-氨基乙氧基二苯硼酸（2-APB，100 microM）或钙螯合剂乙二醇双(2-氨基乙氧基)四乙酸（BAPTA，10 microM）也可阻断。用LPC刺激U937细胞不会导致其对未刺激的EC的黏附增加。
结论
内皮BK(Ca)的激活在单核细胞与内皮细胞的黏附中起重要作用。
Zotero 插件