| Autor: |
Sierro, Frederic, Biben, Christine, Martinez-Muñoz, Laura, Mellado, Mario, Ransohoff, Richard M., Meizhang Li, Woehl, Blanche, Leung, Helen, Groom, Joanna, Batten, Marcel, Harvey, Richard P., Martinez, Carlos, Mackay, Charles R., Mackay, Fabienne |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 9/11/2007, Vol. 104 Issue 37, p14759-14764, 6p, 4 Diagrams, 3 Graphs |
| Abstrakt: |
Chemotactic cytokines (chemokines) attract immune cells, although their original evolutionary role may relate more closely with embryonic development. We noted differential expression of the chemokine receptor CXCR7 (RDC-1) on marginal zone B cells, a cell type associated with autoimmune diseases. We generated Cxcr7-/- mice but found that CXCR7 deficiency had little effect on B cell composition. However, most Cxcr7-/- mice died at birth with ventricular septal defects and semilunar heart valve malformation. Conditional deletion of Cxcr7 in endothelium, using Tie2-Cre transgenic mice, recapitulated this phenotype. Gene profiling of Cxcr7-/- heart valve leaflets revealed a defect in the expression of factors essential for valve formation, vessel protection, or endothelial cell growth and survival. We confirmed that the principal chemokine ligand for CXCR7 was CXCL12/SDF-1, which also binds CXCR4. CXCL12 did not induce signaling through CXCR7; however, CXCR7 formed functional heterodimers with CXCR4 and enhanced CXCL12-induced signaling. Our results reveal a specialized role for CXCR7 in endothelial biology and valve development and highlight the distinct developmental role of evolutionary conserved chemokine receptors such as CXCR7 and CXCR4. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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