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Angiogenesis

Erschienen in:

01.12.2007 | Original Paper

Duffy antigen/receptor for chemokines (DARC) attenuates angiogenesis by causing senescence in endothelial cells

verfasst von: Lili Xu, Annette Ashkenazi, Asok Chaudhuri

Erschienen in: Angiogenesis | Ausgabe 4/2007

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Abstract

Duffy antigen/receptor for chemokines (DARC), expressed on erythrocytes and post-capillary venular endothelial cells, selectively binds both CXC and CC chemokines. DARC binds ELR + angiogenic chemokines such as IL-8 (CXCL8). We show that the DARC on endothelial cells plays a direct role in regulating angiogenesis. Matrigel^TM in vivo plug assay showed that there was more capillary formation in DARC knockout mice compared to wild type mice indicating that DARC attenuated angiogenic activity. In vitro angiogenic assay on Matrigel^TM coated plates using DARC expressing stable human cerebro-microvascular endothelial cells (HCEC) showed that, although capillary formation in transfected cells started early within 4–8 h; capillary formation was attenuated within 12–24 h. Contrarily, mock transfected cells continued to show vascular capillary formation during that time without demonstrating any attenuation. Preincubation of DARC-expressing HCEC with monoclonal antibody (mAb-Fy6) against the N-terminal chemokine-binding domain of DARC increased capillary formation in vitro. Moreover, addition of excess IL-8 during incubation had the similar effect. DARC-expressing transfected endothelial cells underwent senescence in conditioned medium, whereas DARC non-expressing cells remained healthy. Interestingly, after several days in the conditioned medium, DARC expressing senescent cells started to initiate capillary formation; whereas capillary formed with DARC non-expressing cells remained the same. Our data evidently demonstrated that DARC on endothelial cells attenuated the angiogenic activity by causing senescence.

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Titel: Duffy antigen/receptor for chemokines (DARC) attenuates angiogenesis by causing senescence in endothelial cells
verfasst von: Lili Xu
Annette Ashkenazi
Asok Chaudhuri
Publikationsdatum: 01.12.2007
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 4/2007
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-007-9084-y

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