Juremalm M, Olsson N, Nilsson G
Research Group on Mast Cell Biology, Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Clin Exp Allergy. 2005 Jun;35(6):708-12. doi: 10.1111/j.1365-2222.2005.02203.x.
Mast cells (MCs) accumulate at sites of allergic mucosal inflammation where they act as central effectors and regulatory cells. Chemokines are believed to be crucial for the recruitment of MCs to sites of inflammation. We recently reported that human umbilical cord blood MCs (CBMCs) expresses the CC chemokine receptors, CCR1 and CCR4. We found a unique response profile to ligands of the respective receptors in which, of all tested ligands, only CCL5/RANTES-induced migration.
To further investigate the function of CCR4 in MCs.
CBMCs were used for competition binding experiments, migration, and intracellular calcium mobilization and release response studies.
The natural ligands for CCR4, CCL17/TARC and CCL22/MDC could both compete for binding with radiolabelled CCL5. Further, both CCL17 and CCL22 act as CCR4 antagonists by inhibiting CCL5-induced migration. Although both CCL17 and CCL22 caused mobilization of intracellular calcium, none of them induced migration or histamine release.
These results suggest that CCL5-induced migration of MCs via CCR4 can be regulated by the natural agonists CCL17 and CCL22, which are up-regulated at sites of allergic inflammation.
肥大细胞（MCs）在过敏性黏膜炎症部位积聚，在那里它们作为主要效应细胞和调节细胞发挥作用。趋化因子被认为对MCs募集到炎症部位至关重要。我们最近报道，人脐带血MCs（CBMCs）表达CC趋化因子受体CCR1和CCR4。我们发现了对相应受体配体的独特反应模式，在所有测试的配体中，只有CCL5/趋化因子调节激活正常T细胞表达和分泌的因子（RANTES）诱导迁移。
进一步研究CCR4在MCs中的功能。
CBMCs用于竞争结合实验、迁移以及细胞内钙动员和释放反应研究。
CCR4的天然配体CCL17/胸腺活化调节趋化因子（TARC）和CCL22/巨噬细胞来源的趋化因子（MDC）都能与放射性标记的CCL5竞争结合。此外，CCL17和CCL22都通过抑制CCL5诱导的迁移而作为CCR4拮抗剂。虽然CCL17和CCL22都引起细胞内钙的动员，但它们都不诱导迁移或组胺释放。
这些结果表明，CCL5通过CCR4诱导的MCs迁移可由天然激动剂CCL17和CCL22调节，它们在过敏性炎症部位上调。
