PMID- 19577661
OWN - NLM
STAT- MEDLINE
DCOM- 20100615
LR  - 20091102
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 41
IP  - 12
DP  - 2009 Dec
TI  - Anti-HLA I antibodies induce VEGF production by endothelial cells, which 
      increases proliferation and paracellular permeability.
PG  - 2422-30
LID - 10.1016/j.biocel.2009.06.009 [doi]
AB  - Anti-human leukocyte antigen class I (HLA I) antibodies were shown to activate 
      several protein kinases in endothelial cells (ECs), which induces proliferation 
      and cell survival. An important phenomenon in antibody-mediated rejection is the 
      occurrence of interstitial edema. We investigated the effect of anti-HLA I 
      antibodies on endothelial proliferation and permeability, as one possible 
      underlying mechanism of edema formation. HLA I antibodies increased the 
      permeability of cultured ECs isolated from umbilical veins. Anti-HLA I antibodies 
      induced the production of vascular endothelial growth factor (VEGF) by ECs, which 
      activated VEGF receptor 2 (VEGFR2) in an autocrine manner. Activated VEGFR2 led 
      to a c-Src-dependent phosphorylation of vascular endothelial (VE)-cadherin and 
      its degradation. Aberrant VE-cadherin expression resulted in impaired adherens 
      junctions, which might lead to increased endothelial permeability. This effect 
      was only observed after cross-linking of HLA I molecules by intact antibodies. 
      Furthermore, our results suggest that increased endothelial proliferation 
      following anti-HLA I treatment occurs via autocrine VEGFR2 activation. Our data 
      indicate the ability of anti-HLA I to induce VEGF production in ECs. 
      Transactivation of VEGFR2 leads to increased EC proliferation and paracellular 
      permeability. The autocrine effect of VEGF on endothelial permeability might be 
      an explanation for the formation of interstitial edema after transplantation.
FAU - Bieri, Michael
AU  - Bieri M
AD  - Laboratory of Heart Transplantation Immunology, Swiss Cardiovascular Center, 
      Inselspital, University of Bern, 3010 Bern, Switzerland.
FAU - Oroszlan, Melinda
AU  - Oroszlan M
FAU - Farkas, Aniko
AU  - Farkas A
FAU - Ligeti, Nathalie
AU  - Ligeti N
FAU - Bieri, Jurg
AU  - Bieri J
FAU - Mohacsi, Paul
AU  - Mohacsi P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090703
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Antibodies)
RN  - 0 (Cadherins)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Antibodies/*pharmacology
MH  - Cadherins/*biosynthesis/genetics
MH  - Cell Membrane Permeability/drug effects/immunology
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Edema/immunology
MH  - Endothelial Cells/drug effects/immunology/*metabolism/pathology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immunization
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Tight Junctions/drug effects
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics/immunology
MH  - Vascular Endothelial Growth Factor Receptor-2/metabolism
EDAT- 2009/07/07 09:00
MHDA- 2010/06/16 06:00
CRDT- 2009/07/07 09:00
PHST- 2009/03/10 00:00 [received]
PHST- 2009/05/30 00:00 [revised]
PHST- 2009/06/29 00:00 [accepted]
PHST- 2009/07/07 09:00 [entrez]
PHST- 2009/07/07 09:00 [pubmed]
PHST- 2010/06/16 06:00 [medline]
AID - S1357-2725(09)00190-3 [pii]
AID - 10.1016/j.biocel.2009.06.009 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2009 Dec;41(12):2422-30. doi: 
      10.1016/j.biocel.2009.06.009. Epub 2009 Jul 3.