Anti-HLA I antibodies induce VEGF production by endothelial cells, which increases proliferation and paracellular permeability

Bieri, Michael; Oroszlan, Melinda; Farkas, Anikò; Ligeti, Nathalie; Bieri, Jürg; Mohacsi, Paul (2009). Anti-HLA I antibodies induce VEGF production by endothelial cells, which increases proliferation and paracellular permeability. International journal of biochemistry & cell biology, 41(12), pp. 2422-30. Amsterdam: Elsevier 10.1016/j.biocel.2009.06.009

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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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Mohacsi, Paul








Factscience Import

Date Deposited:

04 Oct 2013 15:09

Last Modified:

04 May 2014 23:22

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Web of Science ID:


URI: (FactScience: 194557)

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