Heme oxygenase-1 modulates CD62E-dependent endothelial cell–monocyte interactions and mitigates HLA-I-induced transplant vasculopathy in mice

Frontiers in Immunology, vol. 16, pp. 1447319

Abstract

production of donor-specific antibodies (DSAs) binding to endothelial cells (ECs) within the graft's vasculature. Diverse leukocyte populations recruited into the vessel wall via activated ECs contribute to vascular inflammation. Subsequent smooth muscle cell proliferation results in intima hyperplasia, the pathophysiological correlate of TV. We demonstrated that incubating aortic EC with anti-HLA-I antibodies led to increased monocyte adhesion to and transmigration across an EC monolayer. Both occurred in a CD62E-dependent fashion and were sensitive toward the anti-inflammatory enzyme heme oxygenase (HO)-1 modulation. Using a murine heterotopic aortic transplantation model, we demonstrated that anti-MHC I antibody-induced TV is ameliorated by pharmacologically induced HO-1 and the application of anti-CD62E antibodies results in a deceleration of developing TV. HO-1 modulation is a promising therapeutic approach to prevent leukocyte recruitment and subsequent intima hyperplasia in TV and thus precludes organ failure.

Authors 9

1. Laura Christine Schuster

   Heidelberg University · University Hospital Heidelberg

   Affiliation as printed

   Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany

   Faculty of Biosciences, Heidelberg University, Heidelberg, Germany

2. Marcin Zaradzki

   Heidelberg University · University Hospital Heidelberg

   Affiliation as printed

   Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany

3. Henrike Janssen

   Heidelberg University · University Hospital Heidelberg

   Affiliation as printed

   Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany

4. Nadia Gallenstein

   Heidelberg University · University Hospital Heidelberg

   Affiliation as printed

   Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany

5. Melanie Etheredge Aachen Department of Anesthesiology

   Heidelberg University · University Hospital Heidelberg · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany

   Department of Anesthesiology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany

6. Ilse Hofmann

   German Cancer Research Center

   Affiliation as printed

   Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, Germany

7. Markus A. Weigand

   Heidelberg University · University Hospital Heidelberg

   Affiliation as printed

   Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany

8. Stephan Immenschuh

   Medizinische Hochschule Hannover

   Affiliation as printed

   Department of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany

9. Jan Larmann corresponding Aachen Department of Anesthesiology

   Heidelberg University · University Hospital Heidelberg · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany

   Department of Anesthesiology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany