Enhanced platelet adhesion induces angiogenesis in intestinal inflammation and inflammatory bowel disease microvasculature
| العنوان: | Enhanced platelet adhesion induces angiogenesis in intestinal inflammation and inflammatory bowel disease microvasculature |
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| المؤلفون: | Antonino Spinelli, Silvio Danese, Alessandro Repici, Sergio Rutella, Alberto Malesci, Stefania Vetrano, Raimondo De Cristofaro, Andreas Sturm, Carmen Correale, Cristina Graziani |
| المساهمون: | Rutella, S., Vetrano, S., Correale, C., Graziani, C., Sturm, A., Spinelli, A., De Cristofaro, R., Repici, A., Malesci, A., Danese, S. |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Blackwell Publishing Ltd, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Blood Platelets, Male, Vascular Endothelial Growth Factor A, Angiogenesis, Intercellular Adhesion Molecule-1, CD40 Ligand, Vascular Cell Adhesion Molecule-1, Enzyme-Linked Immunosorbent Assay, Biology, Thromboplastin, Neovascularization, angiogenesis, tumour necrosis factor, Platelet Adhesiveness, Intestinal mucosa, inflammatory bowel disease, medicine, Humans, Cells, Cultured, Inflammation, Integrin alphaVbeta3, Neovascularization, Pathologic, Cell adhesion molecule, Chemokine CX3CL1, Tumor Necrosis Factor-alpha, Endothelial Cells, Cell Biology, Articles, Intercellular adhesion molecule, Inflammatory Bowel Diseases, Coculture Techniques, Intestines, Vascular endothelial growth factor A, Microscopy, Fluorescence, inflammation, Immunology, Microvessels, Cancer research, Molecular Medicine, Female, medicine.symptom |
| الوصف: | 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 α(v) β(3) , 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, α(v) β(3) 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 α(v) β(3) 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 α(v) β(3) , 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1582-4934 1582-1838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0753eed9db74c7e0fb5c9b832bfd89c2Test http://europepmc.org/articles/PMC3922384Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0753eed9db74c7e0fb5c9b832bfd89c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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