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C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance

In the context of transplantation, complement activation is associated with poor prognosis and outcome. While complement activation in antibody-mediated rejection is well-known, less is known about complement activation in acute T cell-mediated rejection (TCMR). There is increasing evidence that com...

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Autores principales: Reuter, Stefan, Kentrup, Dominik, Grabner, Alexander, Köhler, Gabriele, Buscher, Konrad, Edemir, Bayram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700759/
https://www.ncbi.nlm.nih.gov/pubmed/34944007
http://dx.doi.org/10.3390/cells10123499
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author Reuter, Stefan
Kentrup, Dominik
Grabner, Alexander
Köhler, Gabriele
Buscher, Konrad
Edemir, Bayram
author_facet Reuter, Stefan
Kentrup, Dominik
Grabner, Alexander
Köhler, Gabriele
Buscher, Konrad
Edemir, Bayram
author_sort Reuter, Stefan
collection PubMed
description In the context of transplantation, complement activation is associated with poor prognosis and outcome. While complement activation in antibody-mediated rejection is well-known, less is known about complement activation in acute T cell-mediated rejection (TCMR). There is increasing evidence that complement contributes to the clearance of apoptotic debris and tissue repair. In this regard, we have analysed published human kidney biopsy transcriptome data clearly showing upregulated expression of complement factors in TCMR. To clarify whether and how the complement system is activated early during acute TCMR, experimental syngeneic and allogeneic renal transplantations were performed. Using an allogeneic rat renal transplant model, we also observed upregulation of complement factors in TCMR in contrast to healthy kidneys and isograft controls. While staining for C4d was positive, staining with a C3d antibody showed no C3d deposition. FACS analysis of blood showed the absence of alloantibodies that could have explained the C4d deposition. Gene expression pathway analysis showed upregulation of pro-apoptotic factors in TCMR, and apoptotic endothelial cells were detected by ultrastructural analysis. Monocytes/macrophages were found to bind to and phagocytise these apoptotic cells. Therefore, we conclude that early C4d deposition in TCMR may be relevant to the clearance of apoptotic cells.
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spelling pubmed-87007592021-12-24 C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance Reuter, Stefan Kentrup, Dominik Grabner, Alexander Köhler, Gabriele Buscher, Konrad Edemir, Bayram Cells Article In the context of transplantation, complement activation is associated with poor prognosis and outcome. While complement activation in antibody-mediated rejection is well-known, less is known about complement activation in acute T cell-mediated rejection (TCMR). There is increasing evidence that complement contributes to the clearance of apoptotic debris and tissue repair. In this regard, we have analysed published human kidney biopsy transcriptome data clearly showing upregulated expression of complement factors in TCMR. To clarify whether and how the complement system is activated early during acute TCMR, experimental syngeneic and allogeneic renal transplantations were performed. Using an allogeneic rat renal transplant model, we also observed upregulation of complement factors in TCMR in contrast to healthy kidneys and isograft controls. While staining for C4d was positive, staining with a C3d antibody showed no C3d deposition. FACS analysis of blood showed the absence of alloantibodies that could have explained the C4d deposition. Gene expression pathway analysis showed upregulation of pro-apoptotic factors in TCMR, and apoptotic endothelial cells were detected by ultrastructural analysis. Monocytes/macrophages were found to bind to and phagocytise these apoptotic cells. Therefore, we conclude that early C4d deposition in TCMR may be relevant to the clearance of apoptotic cells. MDPI 2021-12-10 /pmc/articles/PMC8700759/ /pubmed/34944007 http://dx.doi.org/10.3390/cells10123499 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Reuter, Stefan
Kentrup, Dominik
Grabner, Alexander
Köhler, Gabriele
Buscher, Konrad
Edemir, Bayram
C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance
title C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance
title_full C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance
title_fullStr C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance
title_full_unstemmed C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance
title_short C4d Deposition after Allogeneic Renal Transplantation in Rats Is Involved in Initial Apoptotic Cell Clearance
title_sort c4d deposition after allogeneic renal transplantation in rats is involved in initial apoptotic cell clearance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700759/
https://www.ncbi.nlm.nih.gov/pubmed/34944007
http://dx.doi.org/10.3390/cells10123499
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