Role of Ca(2+)influx in tissue factor expression in monocyte adhesion to endothelial cells.
Tissue factor (TF) is the primary initiator of the coagulation cascade. Ca(2+) signaling is involved in TF gene expression. Monocyte chemoattractant protein-1 (MCP-1) and its receptor (CCR2) play a pivotal role in the inflammation of atherosclerosis. Although nitric oxide (NO) impairment appears to promote thrombogenicity in monocyte adhesion to endothelial cells (ECs), little is known about its mechanism. N(omega)-nitro-L-arginine methyl ester (L-NAME) promoted MCP-1 expression in EC culture. In response to monocyte adhesion, increased TF expression accompanied by NF-kappaB p65 activation was observed in L-NAME-treated ECs compared with non-treated ECs. This increased TF expression was prevented by BAPTA-AM, an intracellular Ca(2+) chelator. Monocyte attachment to L-NAME- treated ECs increased Ca(2+) influx compared with non-treated ECs, which was prevented by the blockade of MCP1/CCR2. These findings suggest that increased production of MCP-1 caused by L-NAME contributes to the enhancement of Ca(2+) influx only when monocytes adhered to ECs and that this may accelerate TF expression in ECs triggered by monocyte adhesion. We demonstrate the role of Ca(2+) influx via MCP-1/CCR2 under NO impairment in TF expression in monocyte-EC interaction.
Sakamoto
Takayuki
T
First Department of Internal Medicine, Fukushima Medical University, Hikarigaoka, Fukushima, Japan. sakamoto@fmu.ac.jp
Ishibashi
Toshiyuki
T
Maruyama
Yukio
Y
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D009000:Monocytes / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D009569:Nitric Oxide; D013925:Thromboplastin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester