PMID- 26690352
OWN - NLM
STAT- MEDLINE
DCOM- 20160624
LR  - 20190816
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell 
      Activation.
PG  - e0145306
LID - 10.1371/journal.pone.0145306 [doi]
LID - e0145306
AB  - 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 human macro- 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.
FAU - Zilian, Eva
AU  - Zilian E
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Saragih, Hendry
AU  - Saragih H
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
AD  - Faculty of Biology, Gadjah Mada University, Yogyakarta, Indonesia.
FAU - Vijayan, Vijith
AU  - Vijayan V
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Hiller, Oliver
AU  - Hiller O
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Figueiredo, Constanca
AU  - Figueiredo C
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Aljabri, Abid
AU  - Aljabri A
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Blasczyk, Rainer
AU  - Blasczyk R
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Theilmeier, Gregor
AU  - Theilmeier G
AD  - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical 
      School, Hannover, Germany.
FAU - Becker, Jan Ulrich
AU  - Becker JU
AD  - Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
FAU - Larmann, Jan
AU  - Larmann J
AD  - Department of Anesthesiology and Intensive Care Medicine, Hannover Medical 
      School, Hannover, Germany.
FAU - Immenschuh, Stephan
AU  - Immenschuh S
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151221
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (ICAM1 protein, human)
RN  - 0 (Interleukin-8)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 1.14.14.18 (HMOX1 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Antibodies, Monoclonal, Murine-Derived/*pharmacology
MH  - Chemokine CCL2/biosynthesis
MH  - Heme Oxygenase-1/*metabolism
MH  - *Histocompatibility Antigens Class I
MH  - Human Umbilical Vein Endothelial Cells/cytology/*enzymology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Interleukin-8/biosynthesis
MH  - Vascular Cell Adhesion Molecule-1/biosynthesis
PMC - PMC4686182
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/12/23 06:00
MHDA- 2016/06/25 06:00
PMCR- 2015/12/21
CRDT- 2015/12/23 06:00
PHST- 2015/07/17 00:00 [received]
PHST- 2015/12/01 00:00 [accepted]
PHST- 2015/12/23 06:00 [entrez]
PHST- 2015/12/23 06:00 [pubmed]
PHST- 2016/06/25 06:00 [medline]
PHST- 2015/12/21 00:00 [pmc-release]
AID - PONE-D-15-31434 [pii]
AID - 10.1371/journal.pone.0145306 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 21;10(12):e0145306. doi: 10.1371/journal.pone.0145306. 
      eCollection 2015.