Bénard Alan, Boué Jérôme, Chapey Emmanuelle, Jaume Martial, Gomes Bruno, Dietrich Gilles
INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
J Neuroimmunol. 2008 Jun 15;197(1):21-8. doi: 10.1016/j.jneuroim.2008.03.020. Epub 2008 May 16.
Endogenous opioid peptides are locally produced at the inflammatory site where antigens are captured and processed by dendritic cells (DCs). Subsequently, maturing DCs migrate towards draining lymph nodes to initiate T cell response. Given the primordial role of DCs in adaptive immune response, we examined whether opioids may affect the migratory response of DCs. We found that the delta opioid receptor (DOR) mRNA was expressed at low level in bone marrow-derived immature DCs and up-regulated upon DC maturation. Moreover, DOR agonists triggered DC chemotaxis in vitro. In vivo, enkephalins prevented the egress of mature DCs injected into the peritoneal cavity of normal mice. This effect was inhibited by blocking opioid receptors on mature DCs. The cross-talk between CCR7 and DOR receptors that are both up-regulated during DC maturation was then examined. Whereas opioids did not alter the migratory responsiveness to CCR7 ligands, DOR-mediated mobilization of mature DCs was inhibited by CCL19 and CCL21 suggesting that the opioid chemotactic activity decreases as the concentration of the chemokines increases.
内源性阿片肽在炎症部位局部产生，抗原在该部位被树突状细胞（DCs）捕获并处理。随后，成熟的DCs迁移至引流淋巴结以启动T细胞反应。鉴于DCs在适应性免疫反应中的首要作用，我们研究了阿片类物质是否会影响DCs的迁移反应。我们发现，δ阿片受体（DOR）mRNA在骨髓来源的未成熟DCs中低水平表达，在DCs成熟时上调。此外，DOR激动剂在体外触发DCs趋化作用。在体内，脑啡肽可阻止注入正常小鼠腹腔的成熟DCs流出。这种作用可通过阻断成熟DCs上的阿片受体来抑制。然后研究了在DCs成熟过程中均上调的CCR7和DOR受体之间的相互作用。虽然阿片类物质不会改变对CCR7配体的迁移反应性，但CCL19和CCL21可抑制DOR介导的成熟DCs动员，这表明随着趋化因子浓度增加，阿片类物质的趋化活性降低。
