Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration
Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by w...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2010/751313 |
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| author | Thomas Walcher Peter Bernhardt Dusica Vasic Helga Bach Renate Durst Wolfgang Rottbauer Daniel Walcher |
| author_facet | Thomas Walcher Peter Bernhardt Dusica Vasic Helga Bach Renate Durst Wolfgang Rottbauer Daniel Walcher |
| author_sort | Thomas Walcher |
| collection | DOAJ |
| description | Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0±0.1 fold increase in cell migration (P<.01; n=7). Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2±0.1 fold induction at 0.1 µmol/L ivabradine (P<.01 compared to SDF-1-treated cells, n=7). The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC). Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Conclusion. Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect. |
| format | Article |
| id | doaj-art-c422c86378024abfa97b5bab3523b3de |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-c422c86378024abfa97b5bab3523b3de2025-08-20T03:23:11ZengWileyMediators of Inflammation0962-93511466-18612010-01-01201010.1155/2010/751313751313Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte MigrationThomas Walcher0Peter Bernhardt1Dusica Vasic2Helga Bach3Renate Durst4Wolfgang Rottbauer5Daniel Walcher6Department of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Strareß8, 89081 Ulm, GermanyDepartment of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Strareß8, 89081 Ulm, GermanyDepartment of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Strareß8, 89081 Ulm, GermanyDepartment of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Strareß8, 89081 Ulm, GermanyDepartment of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Strareß8, 89081 Ulm, GermanyDepartment of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Strareß8, 89081 Ulm, GermanyDepartment of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Strareß8, 89081 Ulm, GermanyAims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0±0.1 fold increase in cell migration (P<.01; n=7). Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2±0.1 fold induction at 0.1 µmol/L ivabradine (P<.01 compared to SDF-1-treated cells, n=7). The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC). Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Conclusion. Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect.http://dx.doi.org/10.1155/2010/751313 |
| spellingShingle | Thomas Walcher Peter Bernhardt Dusica Vasic Helga Bach Renate Durst Wolfgang Rottbauer Daniel Walcher Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration Mediators of Inflammation |
| title | Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration |
| title_full | Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration |
| title_fullStr | Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration |
| title_full_unstemmed | Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration |
| title_short | Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration |
| title_sort | ivabradine reduces chemokine induced cd4 positive lymphocyte migration |
| url | http://dx.doi.org/10.1155/2010/751313 |
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