Effects of Adiponectin in Heart and Kidney Transplants
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| Language: | English |
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Cleveland State University / OhioLINK
2016
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-csu14837266629771292021-08-03T06:39:36Z Effects of Adiponectin in Heart and Kidney Transplants Danturti, Sreedevi Immunology Adiponectin is a pleiotropic cytokine with diverse immunomodulatory effects on macrophages and lymphocytes. Originally described as being produced exclusively by adipose tissue, adiponectin has more recently been found to be produced by endothelial cells, smooth muscle cells, cardiac myocytes, skeletal muscle, and epithelial cells. More recently, macrophages and lymphocytes have been found to produce adiponectin. In healthy individuals adiponectin circulates in large amounts. Decreased adiponectin levels are associated clinically with cardiovascular disease and type 2 diabetes. Adiponectin binds to two signaling receptors: ADIPOR1 and ADIPOR2. To dissect the impact of local and systemic sources of adiponectin, we transplanted hearts between informative combinations of adiponectin knockout mice. Our experiments support the novel concept that over time CD4+ T cells evolve into a major source of adiponectin that regulates the development of chronic inflammation in coronary arteries. The evidence that T cells produce significant amounts of adiponectin is based on three experimental approaches: First, CD4+ T cells isolated from the blood and spleen after cardiac transplantation express mRNA for adiponectin. Second, reconstitution of T cell deficient recipients with transgenic CD4+ T cells that express receptors for donor antigens results in arterial infiltrates containing T cells and increased adiponectin production in cardiac transplants. Third, hearts from donors genetically deficient for adiponectin express mRNA for adiponectin as inflammation progresses after transplantation to wild type recipients. Taken together these data indicate that adiponectin competent cells originating in the recipient migrate into the transplant. T cell and macrophage infiltrates progressively increased with time after transplantation in renal allografts. At 28 days adiponectin expression was increased in the allografts of wild type but not knockout recipients. CD4+ T cells from wild type recipients expressed adiponectin in the allograft and secreted adiponectin in vitro. In the absence of adiponectin, T cells expressed less negative co-stimulatory molecules and markers of kidney injury increased significantly. Our data suggest that circulating wild type leukocytes express adiponectin and infiltration of adiponectin expressing cells modulates allograft rejection. Establishing T cells as a source of adiponectin provides a new dimension to the modulatory effects of adiponectin on immune responses. 2016 English text Cleveland State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129 http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Immunology |
| spellingShingle |
Immunology Danturti, Sreedevi Effects of Adiponectin in Heart and Kidney Transplants |
| author |
Danturti, Sreedevi |
| author_facet |
Danturti, Sreedevi |
| author_sort |
Danturti, Sreedevi |
| title |
Effects of Adiponectin in Heart and Kidney Transplants |
| title_short |
Effects of Adiponectin in Heart and Kidney Transplants |
| title_full |
Effects of Adiponectin in Heart and Kidney Transplants |
| title_fullStr |
Effects of Adiponectin in Heart and Kidney Transplants |
| title_full_unstemmed |
Effects of Adiponectin in Heart and Kidney Transplants |
| title_sort |
effects of adiponectin in heart and kidney transplants |
| publisher |
Cleveland State University / OhioLINK |
| publishDate |
2016 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129 |
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AT danturtisreedevi effectsofadiponectininheartandkidneytransplants |
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1719440910365753344 |