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AG Immenschuh


Transplant rejection / Heme oxygenase-1 and inflammation



Institut für Transfusionsmedizin

Medizinische Hochschule Hannover

Carl-Neuberg-Str. 1

30625 Hannover

Tel.: +49 (511) 532 6704

Fax: +49 (511) 532 2079

E-Mail: Immenschuh.Stephanmh-hannover.de



Group members



1)  Transplant rejection

 

Transplant rejection plays a major role for the clinical success of solid organ transplantation. Cellular and humoral immunological mechanisms contribute to the pathogenesis of rejection after transplantation of organs such as kidney and heart. Specifically, antibody-mediated rejection (ABMR) is critical for the clinical outcome of allograft transplantation. ABMR is primarily mediated by donor specific-antibodies against antigens of the major histocompatibility complex (MHC), which is known as the human leukocyte antigen (HLA) system in humans.

In current projects we study the mechanisms how MHC antibodies are generated in allograft transplantation and how these antibodies may mediate rejection. To this end complement-dependent and -independent mechanisms of antibodies, eg. via direct cellular interactions with allograft vascular endothelial cells, are studied by various in vitro and in vivo approaches.

2)  Heme oxygenase-1 and inflammation

 

Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of heme degradation. HO-1, which is highly up-regulated by numerous stress stimuli, has major antioxidant, anti-inflammatory and immunomodulatory functions. Anti-inflammatory effects of HO-1 are mediated via catalytic breakdown of pro-inflammatory ‘free’ heme and production of antioxidant and anti-inflammatory carbon monoxide and biliverdin, which is enzymatically converted to bilirubin. Notably, cell-type specific functions of HO-1 in mononuclear phagocytes (monocytes, macrophages) and in endothelial cells appear to be of critical physiological and pathophysiological significance. HO-1 regulation is controlled via a complex network of signaling cascades including the interplay of the master antioxidant transcription factor nuclear factor-E2-related factor-2 (Nrf2) and the nuclear repressor protein BTB domain and CNC homologue-1 (Bach1). A major goal of our work is to better understand the mechanisms of HO-1 regulation and its anti-inflammatory functions to develop novel therapeutic strategies for the treatment of inflammatory disorders.

 

  

 

  

 Funding:

DFG

Project ID IM 20/4-1

2015-2020

BMBF (DAAD)

Project ID 57317676

2017-2018

EFRE (EU)

Project ID ZW 6-85007634

2017-2020

 

 

Publikationen in PubMed