Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro  

作　　者：Zhi LI Tao SONG Gui-zhen LIU Li-ying LIU 

机构地区：[1]Department of Pharmacology, Pharmaceutical College, Central South University, Changsha 410078, China

出　　处：《Acta Pharmacologica Sinica》2006年第10期1326-1332,共7页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(No 39770857).

摘　　要：Aim： To explore the effects of cariporide on the expression of intercellular adhesion molecule-1 （ICAM-1） and the adhesion of monocytes to vascular smooth muscle cells （SMC） in vitro. Methods： Monocytes were isolated from human peripheral blood by the Ficoll-Hypaque method. The expression of ICAM- 1 in SMC was detected by ELISA. The adhesion of monocytes to SMC was stimulated by lysophosphatidylcholine （LPC）. The adhesion ratio of monocytes was assayed by measuring protein contents. The intracellular pH （[pH]i） of SMC was measured with 2＇,7＇-bis（2-carboxyethyl）-5,6-carboxyfluorescein （BCECF）. Results： Preincubation of SMC with LPC alone （5 lag/mL） for 4 h markedly enhanced the expression of ICAM-1 in SMC and the rate of the adhesion of monocytes to SMC in a concentration-dependent and time-related manner. LPC simultaneously also induced an increase of [pH]i value in SMC. Cariporide concentration-dependently reduced the adhesion ratio of monocytes to SMC and the expression of ICAM- 1 in SMC induced by LPC. The inhibitory effects of cariporide on the expression of ICAM-1 in SMC and the adhesion of monocytes to SMC also were associated with blocking LPC-induced elevation of the [PH]i value in SMC. Conclusion： LPC-induced monocyte-SMC adhesion may be mediated via activation of the Na^＋/H^＋ （NHE） exchanger. The action mechanism of cariporide may be related with inhibition of activation of the Na^＋/H^＋ exchanger of plasma membranes and ICAM- 1 expression on the surface of SMC induced by LPC.Aim： To explore the effects of cariporide on the expression of intercellular adhesion molecule-1 （ICAM-1） and the adhesion of monocytes to vascular smooth muscle cells （SMC） in vitro. Methods： Monocytes were isolated from human peripheral blood by the Ficoll-Hypaque method. The expression of ICAM- 1 in SMC was detected by ELISA. The adhesion of monocytes to SMC was stimulated by lysophosphatidylcholine （LPC）. The adhesion ratio of monocytes was assayed by measuring protein contents. The intracellular pH （[pH]i） of SMC was measured with 2＇,7＇-bis（2-carboxyethyl）-5,6-carboxyfluorescein （BCECF）. Results： Preincubation of SMC with LPC alone （5 lag/mL） for 4 h markedly enhanced the expression of ICAM-1 in SMC and the rate of the adhesion of monocytes to SMC in a concentration-dependent and time-related manner. LPC simultaneously also induced an increase of [pH]i value in SMC. Cariporide concentration-dependently reduced the adhesion ratio of monocytes to SMC and the expression of ICAM- 1 in SMC induced by LPC. The inhibitory effects of cariporide on the expression of ICAM-1 in SMC and the adhesion of monocytes to SMC also were associated with blocking LPC-induced elevation of the [PH]i value in SMC. Conclusion： LPC-induced monocyte-SMC adhesion may be mediated via activation of the Na^＋/H^＋ （NHE） exchanger. The action mechanism of cariporide may be related with inhibition of activation of the Na^＋/H^＋ exchanger of plasma membranes and ICAM- 1 expression on the surface of SMC induced by LPC.

关 键 词：Na^＋/H^＋ exchanger CARIPORIDE lysophosphati-dylcholine intercellular adhesion molecule-1 monocyte smooth muscle cells 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]