Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice
Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution i...
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MDPI AG
2020-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/5/1650 |
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| author | Subhradip Mukhopadhyay Joel Gabre Christine Chabasse Jonathan S. Bromberg Toni M. Antalis Rajabrata Sarkar |
| author_facet | Subhradip Mukhopadhyay Joel Gabre Christine Chabasse Jonathan S. Bromberg Toni M. Antalis Rajabrata Sarkar |
| author_sort | Subhradip Mukhopadhyay |
| collection | DOAJ |
| description | Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD-1 mice. CD4 and CD8 positive T cells, as determined by flow cytometry, were present in thrombi both during thrombus formation and resolution. Depletion of the CD4 and CD8 positive T cells by antibody treatment selectively impaired thrombus resolution compared to animals treated with isotype control antibodies, without an effect on venous thrombus formation. Quantitation of intra-thrombus macrophage numbers, fibrinolytic marker expression, and gelatinolytic activity by zymography revealed that T cell depletion decreased the number of macrophages, reduced the expression of fibrinolytic marker urokinase plasminogen activator (uPA), and decreased the activity of matrix metalloprotinease-9 (MMP-9). These data implicate CD4 and CD8 positive T cells in functionally contributing to venous thrombus resolution, thus representing a potential therapeutic target, but also underscoring potential risks involved in T cell depletion used clinically for solid organ and hematopoietic transplantation procedures. |
| first_indexed | 2024-04-12T21:26:41Z |
| format | Article |
| id | doaj.art-68c708520ac448d3a78ffde13b2a2128 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T21:26:41Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-68c708520ac448d3a78ffde13b2a21282022-12-22T03:16:08ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01215165010.3390/ijms21051650ijms21051650Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in MiceSubhradip Mukhopadhyay0Joel Gabre1Christine Chabasse2Jonathan S. Bromberg3Toni M. Antalis4Rajabrata Sarkar5Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USAResolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD-1 mice. CD4 and CD8 positive T cells, as determined by flow cytometry, were present in thrombi both during thrombus formation and resolution. Depletion of the CD4 and CD8 positive T cells by antibody treatment selectively impaired thrombus resolution compared to animals treated with isotype control antibodies, without an effect on venous thrombus formation. Quantitation of intra-thrombus macrophage numbers, fibrinolytic marker expression, and gelatinolytic activity by zymography revealed that T cell depletion decreased the number of macrophages, reduced the expression of fibrinolytic marker urokinase plasminogen activator (uPA), and decreased the activity of matrix metalloprotinease-9 (MMP-9). These data implicate CD4 and CD8 positive T cells in functionally contributing to venous thrombus resolution, thus representing a potential therapeutic target, but also underscoring potential risks involved in T cell depletion used clinically for solid organ and hematopoietic transplantation procedures.https://www.mdpi.com/1422-0067/21/5/1650peripheral vascular diseaset cellscd4cd8thrombus resolutionmatrix metalloproteinasemacrophage |
| spellingShingle | Subhradip Mukhopadhyay Joel Gabre Christine Chabasse Jonathan S. Bromberg Toni M. Antalis Rajabrata Sarkar Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice International Journal of Molecular Sciences peripheral vascular disease t cells cd4 cd8 thrombus resolution matrix metalloproteinase macrophage |
| title | Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice |
| title_full | Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice |
| title_fullStr | Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice |
| title_full_unstemmed | Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice |
| title_short | Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice |
| title_sort | depletion of cd4 and cd8 positive t cells impairs venous thrombus resolution in mice |
| topic | peripheral vascular disease t cells cd4 cd8 thrombus resolution matrix metalloproteinase macrophage |
| url | https://www.mdpi.com/1422-0067/21/5/1650 |
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