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


CONCLUSIONS
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.
Li
Zhi
Z
Department of Pharmacology, Pharmaceutical College, Central South University, Changsha 410078, China.
Song
Tao
T
Liu
Gui-zhen
GZ
Liu
Li-ying
LY
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008244:Lysophosphatidylcholines; D009000:Monocytes / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D008244:Lysophosphatidylcholines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D018799:Intercellular Adhesion Molecule-1; C093373:cariporide