Endothelial endoglin is involved in inflammation: role in leukocyte adhesion and transmigration
| Autor: | Francisco J. Blanco, Carmen Langa, Luisa María Botella, José M. López-Novoa, Carmelo Bernabeu, Francisco Sanz-Rodríguez, Elisa Rossi, Carlos Cabañas, Nélida Eleno, Annette Düwell |
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| Rok vydání: | 2013 |
| Předmět: |
Chemokine
Angiogenesis Immunology Receptors Cell Surface Biochemistry Mice Chemokine receptor Cell Migration Assays Leukocyte Transcellular Cell Migration Antigens CD hemic and lymphatic diseases Leukocyte Trafficking Cell Adhesion otorhinolaryngologic diseases Animals Humans Stromal cell-derived factor 1 RGD motif Inflammation biology Endoglin Transendothelial and Transepithelial Migration Endothelial Cells Cell Biology Hematology Flow Cytometry Leukocyte extravasation Chemokine CXCL12 Mice Mutant Strains Cell biology Mice Inbred C57BL Chemotaxis Leukocyte Microscopy Fluorescence biology.protein Integrin alpha5beta1 |
| Zdroj: | ResearcherID Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Human endoglin is an RGD-containing transmembrane glycoprotein identified in vascular endothelial cells. Although endoglin is essential for angiogenesis and its expression is up-regulated in inflammation and at sites of leukocyte extravasation, its role in leukocyte trafficking is unknown. This function was tested in endoglin heterozygous mice (Eng+/-) and their wild-type siblings Eng+/+ treated with carrageenan or LPS as inflammatory agents. Both stimuli showed that inflammation-induced leukocyte transendothelial migration to peritoneum or lungs was significantly lower in Eng+/- than in Eng+/+ mice. Leukocyte transmigration through cell monolayers of endoglin transfectants was clearly enhanced in the presence of endoglin. Coating transwells with the RGD-containing extracellular domain of endoglin, enhanced leukocyte transmigration, and this increased motility was inhibited by soluble endoglin. Leukocytes stimulated with CXCL12, a chemokine involved in inflammation, strongly adhered to endoglincoated plates and to endoglin-expressing endothelial cells. This endoglin-dependent adhesion was abolished by soluble endoglin, RGD peptides, the anti-integrin α5β1 inhibitory antibody LIA1/2 and the chemokine receptor inhibitor AMD3100. These results demonstrate for the first time that endothelial endoglin interacts with leukocyte integrin α5β1 via its RGD motif, and this adhesion process is stimulated by the inflammatory chemokine CXCL12, suggesting a regulatory role for endoglin in transendothelial leukocyte trafficking. © 2013 by The American Society of Hematology. Ministerio de Economia y Competitividad of Spain (SAF2010-61 827, SAF2010-15 881); Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER); Red de Investigacion Cooperativa en Enfermedades Renales (REDINDEN) |
| Databáze: | OpenAIRE |
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