β-defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells:: CCR6 is not involved
β-defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells:: CCR6 is not involved
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DOI：
10.1002/eji.200737292
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发表时间：
2007-09-01
影响因子：
5.4
通讯作者：
Zwirner, Joerg
中科院分区：
文献类型：
--
作者：
Soruri, Afsaneh;Grigat, Jasmin;Zwirner, Joerg
-防御素是一种天然的肽类抗生素，其免疫调节功能尚不清楚。在本研究中，发现巨噬细胞利用G α (i)蛋白以及MAPK、ERK、p38和JNK作为信号转导器迁移到人β -防御素(HBD)- 1至-4。此外，肥大细胞对HBD-1 -4的反应是钙通量和趋化性，在IgE +抗原或离子霉素的刺激下增加。相比之下，人β -防御素不能诱导记忆淋巴细胞和树突状细胞（DC）的迁移。与HBD类似，小鼠β -防御素(mBD)-8动员巨噬细胞，缺乏招募记忆T细胞的能力。这些发现是出乎意料的，因为记忆T细胞和DC上的CCR6先前被观察到是人类β -防御素的受体。然而，为了支持我们的发现，RBL-2H3和300.19细胞稳定表达CCR6被证明对HBD-2和-3无反应。有趣的是，我们观察到HBD-1到-4之间的同源脱敏不依赖于pkc，这表明HBD有一个共同的受体。综上所述，巨噬细胞和肥大细胞的趋化作用在p -防御素家族中是进化保守的，尽管它们的序列差异很大，抗菌活性也不同。然而，CCR6并不是β -防御素的功能性受体。
beta-Defensins are natural peptide antibiotics whose immunomodulatory functions are poorly understood. In the present study, macrophages were found to migrate to human beta-defensins (HBD)-l to -4 using G alpha(i) proteins as well as MAPK ERK, p38 and JNK as signal transducers. In addition, mast cells responded to HBD-1 to -4 with calcium fluxes as well as chemotaxis, which increased upon stimulation with IgE plus antigen or ionomycin. In contrast, human beta-defensins were unable to induce migration of memory lymphocytes and dendritic cells (DC). Similar to HBD, the murine beta-defensin (mBD)-8 mobilized macrophages and lacked the ability to recruit memory T cells. These findings were unexpected as CCR6 on memory T cells and DC has been previously observed to be a receptor for human beta-defensins. In support of our findings, however, RBL-2H3 as well as 300.19 cells stably expressing CCR6 proved to be unresponsive to HBD-2 and -3. Intriguingly, our observation of a PKC-independent homologous desensitization between HBD-1 to -4 suggests a common receptor for HBD. In summary, chemoattraction of macrophages and mast cells is evolutionary conserved within the P-defensin family despite a considerable sequence variation and distinct antimicrobial activities. However, CCR6 is not a functional receptor for beta-defensins.