TY  - JOUR
AU  - Schuster, Laura
AU  - Zaradzki, Marcin
AU  - Janssen, Henrike
AU  - Gallenstein, Nadia
AU  - Etheredge, Melanie
AU  - Hofmann, Ilse
AU  - Weigand, Markus A
AU  - Immenschuh, Stephan
AU  - Larmann, Jan
TI  - Heme oxygenase-1 modulates CD62E-dependent endothelial cell-monocyte interactions and mitigates HLA-I-induced transplant vasculopathy in mice.
JO  - Frontiers in immunology
VL  - 16
SN  - 1664-3224
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2025-00625
SP  - 1447319
PY  - 2025
AB  - The main risk factor for developing transplant vasculopathy (TV) after solid organ transplantation is de-novo 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.
KW  - Animals
KW  - Heme Oxygenase-1: metabolism
KW  - Mice
KW  - Endothelial Cells: immunology
KW  - Endothelial Cells: metabolism
KW  - Monocytes: immunology
KW  - Monocytes: metabolism
KW  - Graft Rejection: immunology
KW  - Humans
KW  - Histocompatibility Antigens Class I: immunology
KW  - Histocompatibility Antigens Class I: metabolism
KW  - Cell Communication: immunology
KW  - Mice, Inbred C57BL
KW  - Male
KW  - Disease Models, Animal
KW  - Cell Adhesion: immunology
KW  - Vascular Diseases: immunology
KW  - Vascular Diseases: etiology
KW  - Vascular Diseases: pathology
KW  - Vascular Diseases: metabolism
KW  - accommodation (Other)
KW  - adhesion (Other)
KW  - anti-HLA-1 antibodies (Other)
KW  - chronic rejection (Other)
KW  - endothelial cells (Other)
KW  - heme oxygenase-1 (Other)
KW  - monocyte transmigration (Other)
KW  - transplantation (Other)
KW  - Heme Oxygenase-1 (NLM Chemicals)
KW  - Histocompatibility Antigens Class I (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40124367
C2  - pmc:PMC11925954
DO  - DOI:10.3389/fimmu.2025.1447319
UR  - https://inrepo02.dkfz.de/record/300127
ER  -