Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

C1Q PRODUCTION BY RESIDENT VERSUS INFILTRATING LY6C+ CELLS IN MHC MISMATCHED MURINE KIDNEY TRANSPLANTS

Khedraki, Raneem
http://orcid.org/0009-0005-7552-0080
http://rave.ohiolink.edu/etdc/view?acc_num=csu1698062892360868

Abstract Details

2022, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
Transplantation requires that an organ be removed from the circulation of the donor and then reintroduced to the circulation of the recipient. Organs from deceased donors are often removed from the donor in one hospital and then transported on ice to another hospital for the transplant procedure. Consequently, transplanted organs are subjected to varying periods of ischemia before reperfusion in the recipient. This results in ischemia reperfusion injury (IRI) to the organ. For transplanted kidneys, IRI is frequently severe enough to cause delayed function requiring dialysis and even total failure of the graft. Identifying mechanisms that mediate this injury remains a crucial goal of transplantation. It is known that IRI causes a surge of apoptosis. During normal homeostatic turnover of cells, apoptotic bodies are cleared without inducing inflammation or immune responses by C1q, the initial component of the complement system. In patients with the rare genetic deficiency of C1q, apoptotic bodies are not effectively cleared and immune responses develop to autoantigens in the apoptotic bodies. We examined the role of C1q in modulating the early immune response to IRI in renal transplants by investigating the absence of C1q on early graft injury in an MHC mismatched murine transplant model. We found that A/J kidney grafts transplanted into C1q KO mice exhibited high levels of urinary injury marker, neutrophil gelatinase associated lipocalin (Ngal) within 1 and 2 days posttransplant and decreased survival compared to WT mice. Immunohistology demonstrated increased platelet aggregates in the renal medulla typical of unresolved ischemia induced injury in grafts undergoing early rejection 5 days after transplantation. Sources of C1q were identified during IRI in renal transplants by isolating infiltrating and resident Ly6C+ cell populations from the graft. Resident Ly6C+ cells in the donor kidney were found to express high levels of C1q even 6 days after transplantation. Local availability of C1q could decrease inflammatory responses occurring within the graft and extend graft survival.
William Baldwin, PhD (Committee Chair)
Keith McCrae, MD (Committee Member)
Barsanjit Mazumder, PhD (Committee Member)
Tom McIntyre, PhD (Committee Member)
Trine Jorgensen, PhD (Other)
Anna Valujskikh, PhD (Other)
Biology; Cellular Biology; Immunology; Molecular Biology
C1q; kidney; transplant immunology; transplantation; macrophages; T cells; flow cytometry; nanostring

Recommended Citations

Citations

  • Khedraki, R. (2022). C1Q PRODUCTION BY RESIDENT VERSUS INFILTRATING LY6C+ CELLS IN MHC MISMATCHED MURINE KIDNEY TRANSPLANTS [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1698062892360868

    APA Style (7th edition)

  • Khedraki, Raneem. C1Q PRODUCTION BY RESIDENT VERSUS INFILTRATING LY6C+ CELLS IN MHC MISMATCHED MURINE KIDNEY TRANSPLANTS. 2022. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1698062892360868.

    MLA Style (8th edition)

  • Khedraki, Raneem. "C1Q PRODUCTION BY RESIDENT VERSUS INFILTRATING LY6C+ CELLS IN MHC MISMATCHED MURINE KIDNEY TRANSPLANTS." Doctoral dissertation, Cleveland State University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=csu1698062892360868

    Chicago Manual of Style (17th edition)

csu1698062892360868
85
© 2022, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.
Release 3.2.12