Rutella, S. ORCID: 0000-0003-1970-7375, Vetrano, S., Correale, C., Graziani, C., Sturm, A., Spinelli, A., De Cristofaro, R., Repici, A., Malesci, A. and Danese, S., 2010. Enhanced platelet adhesion induces angiogenesis in intestinal inflammation and inflammatory bowel disease microvasculature. Journal of Cellular and Molecular Medicine-, 15 (3), pp. 625-634. ISSN 1582-1838
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Abstract
Although angiogenesis is viewed as a fundamental component of inflammatory bowel disease (IBD) pathogenesis, we presently lack a thorough knowledge of the cell type(s) involved in its induction and maintenance in the inflamed intestinal mucosa. This study aimed to determine whether platelet (PLT) adhesion to inflamed intestinal endothelial cells of human origin may favour angiogenesis. Unstimulated or thrombin-activated human PLT were overlaid on resting or tumour necrosis factor (TNF)-α-treated human intestinal microvascular endothelial cells (HIMEC), in the presence or absence of blocking antibodies to either vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, integrin αvβ3, tissue factor (TF) or fractalkine (FKN). PLT adhesion to HIMEC was evaluated by fluorescence microscopy, and release of angiogenic factors (VEGF and soluble CD40L) was measured by ELISA. A matrigel tubule formation assay was used to estimate PLT capacity to induce angiogenesis after co-culturing with HIMEC. TNF-α up-regulated ICAM-1, αvβ3 and FKN expression on HIMEC. When thrombin-activated PLT were co-cultured with unstimulated HIMEC, PLT adhesion increased significantly, and this response was further enhanced by HIMEC activation with TNF-α. PLT adhesion to HIMEC was VCAM-1 and TF independent but ICAM-1, FKN and integrin αvβ3 dependent. VEGF and sCD40L were undetectable in HIMEC cultures either before or after TNF-α stimulation. By contrast, VEGF and sCD40L release significantly increased when resting or activated PLT were co-cultured with TNF-α-pre-treated HIMEC. These effects were much more pronounced when PLT were derived from IBD patients. Importantly, thrombin-activated PLT promoted tubule formation in HIMEC, a functional estimate of their angiogenic potential. In conclusion, PLT adhesion to TNF-α-pre-treated HIMEC is mediated by ICAM-1, FKN and αvβ3, and is associated with VEGF and sCD40L release. These findings suggest that inflamed HIMEC may recruit PLT which, upon release of pro-angiogenic factors, actively contribute to inflammation-induced angiogenesis.
Item Type: | Journal article | ||||
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Publication Title: | Journal of Cellular and Molecular Medicine- | ||||
Creators: | Rutella, S., Vetrano, S., Correale, C., Graziani, C., Sturm, A., Spinelli, A., De Cristofaro, R., Repici, A., Malesci, A. and Danese, S. | ||||
Date: | 16 February 2010 | ||||
Volume: | 15 | ||||
Number: | 3 | ||||
ISSN: | 1582-1838 | ||||
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Divisions: | Schools > School of Science and Technology | ||||
Record created by: | Linda Sullivan | ||||
Date Added: | 13 Sep 2016 13:51 | ||||
Last Modified: | 09 Jun 2017 14:05 | ||||
URI: | https://irep.ntu.ac.uk/id/eprint/28506 |
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