Cell cycle–dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity
Paola Romagnani, … , Sergio Romagnani, Mario Serio
Paola Romagnani, … , Sergio Romagnani, Mario Serio
Published January 1, 2001
Citation Information: J Clin Invest. 2001;107(1):53-63. https://doi.org/10.1172/JCI9775.
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Article

Cell cycle–dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity

Abstract

Endothelial cell receptors for the angiostatic chemokines IFN-γ–inducible protein of 10 kDa (IP-10) and monokine induced by IFN-γ (Mig) have not yet been identified, and the mechanisms responsible for the effects of these chemokines on angiogenesis are still unclear. IP-10 and Mig share a common functional receptor on activated T lymphocytes, named CXC chemokine receptor 3 (CXCR3). Using in situ hybridization and immunohistochemistry, we show that CXCR3 is expressed by a small percentage of microvascular endothelial cells in several human normal and pathological tissues. Primary cultures of human microvascular endothelial cells (HMVECs) likewise express CXCR3, although this expression is limited to the S/G2-M phase of their cell cycle. Both IP-10 and Mig, as well as the IFN-γ–inducible T-cell α chemoattractant (I-TAC), which all share high-affinity binding for CXCR3, block HMVEC proliferation in vitro, an effect that can be inhibited by an anti-CXCR3 antibody. These data provide definitive evidence of CXCR3 expression by HMVEC and open new avenues for therapeutic interventions in all conditions in which an angiostatic effect may be beneficial.

Authors

Paola Romagnani, Francesco Annunziato, Laura Lasagni, Elena Lazzeri, Chiara Beltrame, Michela Francalanci, Mariagrazia Uguccioni, Grazia Galli, Lorenzo Cosmi, Lucia Maurenzig, Marco Baggiolini, Enrico Maggi, Sergio Romagnani, Mario Serio

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Figure 2

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CXCR3 mRNA expression by endothelial cells from kidney of patients suffe...
CXCR3 mRNA expression by endothelial cells from kidney of patients suffering from glomerulonephritis. (a) CXCR3 mRNA expression in the kidney biopsy specimen. The section, which was hybridized with 35S-labeled CXCR3 antisense probe, shows positive signal in a vessel wall. ×1,000. (b) Autoradiograph of a consecutive section hybridized with sense CXCR3 probe, showing virtually no signal. ×1,000. (c) Association between CXCR3 mRNA expression and vWF, as shown by combining in situ hybridization with CXCR3 antisense probe (white grains along the vessel wall) and immunohistochemistry with anti-vWF mAb (red) (dark field, ×250). (d) Higher-power magnification (×1,000) of inset in (c) showing both CXCR3 mRNA (black grains) and vWF expression (red). (e) CXCR3 mRNA expression by Th1 cells, used as positive control. The cells were hybridized with antisense CXCR3 probe (dark field, ×250). (f) Autoradiograph of the same Th1 cell culture hybridized with sense CXCR3 probe, showing virtually no signal (dark field, ×250).