Effect of trapidil on effector functions of monocytes related to atherosclerotic plaque.
The infiltration and activation of inflammatory cells play an important role in the formation and stability of coronary atherosclerotic plaque in patients with acute coronary syndrome. In this study, we evaluated the effect of trapidil, an anti-platelet agent, on atheroma-related functions of human T cells and monocytes. Trapidil and anti-CD154 (CD40 ligand) antibody inhibited the increase of procoagulant activity in the mixed lymphocyte reaction; trapidil also suppressed the induction of tissue factor, monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 in the mixed lymphocyte reaction. Trapidil did not alter CD154 expression on isolated T cells, but it diminished CD40 expression on isolated monocytes and human monocytic leukemia THP-1 cells stimulated with interferon-gamma. Moreover, trapidil reduced MCP-1 production of isolated monocytes and THP-1 cells stimulated with interferon-gamma plus CD154-transfected cells. This effect was not seen with other tested anti-platelet agents and coronary vasodilators. In conclusion, trapidil directly acts on monocytes/macrophages to lower their susceptibility to CD154 on T cells.
Kato
Y
Y
Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara, Gotemba, 412-8524, Shizuoka, Japan. yutakato@mochida.co.jp
Tsuda
T
T
Hosaka
Y
Y
Takahashi
T
T
Shirakawa
K
K
Furusako
S
S
Mizuguchi
K
K
Mochizuki
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis / Q000276:immunology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis / Q000187:drug effects; D014192:Trapidil / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D018932:Chemokine CCL2; D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; D007371:Interferon-gamma; D013925:Thromboplastin; D020780:Matrix Metalloproteinase 9; D014192:Trapidil