CCL18 does not require CCR6 for functional activity in mice (44.3)
| Autor: | Sergei Atamas, Irina Luzina |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:44.3-44.3 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | CCL18 is an orphan chemokine present in primates but not in mice. Human CCL18 is fully functional in mice in vivo: it is chemotactic to mouse T lymphocytes similar to its effect on human T cells, suggesting that although mice have lost CCL18 after evolutionary separation from primates, its receptor remains preserved and functional. Attempts to identify CCL18 receptor have been unsuccessful, but a recent study (Am J Respir Crit Care Med 2011, 183:A5574) suggested that CCR6, the receptor for CCL20, is also used by CCL18. To explore this possibility, we administered a replication-deficient recombinant adenoviral construct encoding human CCL18 (AdV-CCL18) to mouse lungs in wild type (WT) and CCR6-deficient (-/-) animals. Non-manipulated as well as AdV-NULL-infected control WT mice had 2-4% of lymphocytes in their bronchoalveolar lavage (BAL), whereas AdV-CCL18-infected WT mice had 20-25 % of BAL lymphocytes. Flowcytometric analyses showed that less than 5% of CD3+ BAL cells in CCL18-expressing WT mice were also CCR6+. Histological changes caused by CCL18 delivery were similar in WT and CCR6 -/- mice, with characteristic perivascular and peribronchial infiltration of T cells which was not observed in AdV-NULL-treated mice. Thus, it appears that human CCL18 utilizes a receptor different than CCR6 in mice. A possibility exists that mice and humans utilize different CCL18 receptors, but it is unlikely considering the remarkable similarity of CCL18 effects on human and mouse cells. |
| Databáze: | OpenAIRE |
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