Universität zu Köln

Zilian, Eva, Saragih, Hendry, Vijayan, Vijith, Hiller, Oliver, Figueiredo, Constanca, Aljabri, Abid, Blasczyk, Rainer ORCID: 0000-0003-3875-3190, Theilmeier, Gregor, Becker, Jan Ulrich ORCID: 0000-0003-2929-8085, Larmann, Jan ORCID: 0000-0003-3365-4572 and Immenschuh, Stephan ORCID: 0000-0003-3722-5791 (2015). Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation. PLoS One, 10 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Antibody-mediated rejection (AMR) is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA) class I (HLA I) antibodies (Abs) play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs). The antioxidant enzyme heme oxygenase (HO)-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary humanmacro- and microvascular ECs treatment with monoclonal pan-and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]). Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO)-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zilian, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Saragih, Hendry UNSPECIFIED UNSPECIFIED UNSPECIFIED Vijayan, Vijith UNSPECIFIED UNSPECIFIED UNSPECIFIED Hiller, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Figueiredo, Constanca UNSPECIFIED UNSPECIFIED UNSPECIFIED Aljabri, Abid UNSPECIFIED UNSPECIFIED UNSPECIFIED Blasczyk, Rainer UNSPECIFIED orcid.org/0000-0003-3875-3190 UNSPECIFIED Theilmeier, Gregor UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jan Ulrich UNSPECIFIED orcid.org/0000-0003-2929-8085 UNSPECIFIED Larmann, Jan UNSPECIFIED orcid.org/0000-0003-3365-4572 UNSPECIFIED Immenschuh, Stephan UNSPECIFIED orcid.org/0000-0003-3722-5791 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-383595
DOI:	10.1371/journal.pone.0145306
Journal or Publication Title:	PLoS One
Volume:	10
Number:	12
Date:	2015
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; MEDIATED ALLOGRAFT-REJECTION; INTRAVENOUS IMMUNE GLOBULIN; CARBON-MONOXIDE; TRANSPLANT VASCULOPATHY; CARDIAC ALLOGRAFTS; OXIDATIVE STRESS; COMPLEMENT; MECHANISMS; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38359