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Thesis Sreedevi Danturti.pdf (2.8 MB)

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Effects of Adiponectin in Heart and Kidney Transplants

Danturti, Sreedevi
http://orcid.org/0000-0003-1471-4752
http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129

Abstract Details

2016, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
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.
William Baldwin, Ph.D. (Advisor)
Trine Jorgensen, Ph.D. (Committee Member)
Ofer Reizes, Ph.D. (Committee Member)
Sailen Barik, Ph.D. (Committee Member)
Barsanjit Mazumder, Ph.D. (Committee Member)
John Kirwan, Ph.D. (Committee Member)
90 p.
Immunology

Recommended Citations

Citations

  • Danturti, S. (2016). Effects of Adiponectin in Heart and Kidney Transplants [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129

    APA Style (7th edition)

  • Danturti, Sreedevi. Effects of Adiponectin in Heart and Kidney Transplants. 2016. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129.

    MLA Style (8th edition)

  • Danturti, Sreedevi. "Effects of Adiponectin in Heart and Kidney Transplants." Doctoral dissertation, Cleveland State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129

    Chicago Manual of Style (17th edition)

csu1483726662977129
270
© 2016, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.