Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment
Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment
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DOI：
10.1016/s1074-7613(00)80334-9
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发表时间：
1997-03-01
期刊：
影响因子：
32.4
通讯作者：
Mantovani, A
中科院分区：
文献类型：
--
作者：
Romano, M;Sironi, M;Mantovani, A
IL-6(-/-)小鼠皮下气囊中的白细胞积累受损。白细胞积聚缺陷并非由于IL-6(-/-)白细胞迁移能力降低所致，而是与趋化因子原位产生减少有关。这些观察导致人们重新审视 IL-6 与内皮细胞 (EC) 的相互作用。 Sc 仅表达 gp130 信号转导链，而不表达亚基特异性 IL-6R，因此对 IL-6 无反应。然而，通过 STATE 的激活、趋化因子表达和 ICAM-1 的增强来测量，EC 对 IL-6 和可溶性 IL-6R 的组合有反应。 IL-6-IL-6R 复合物的激活被 IL-6 受体拮抗剂抑制并被超级激动剂增强。因此，体内和体外证据支持这样的概念：IL-6系统通过放大白细胞募集而在局部炎症反应中发挥意想不到的积极作用。
IL-6(-/-) mice showed impaired leukocyte accumulation in subcutaneous air pouches. Defective leukocyte accumulation was not due to a reduced migratory capacity of IL-6(-/-) leukocytes and was associated with a reduced in situ production of chemokines. These observations led to a reexamination of the interaction of IL-6 with endothelial cells (EC). Sc express only the gp130 signal transducing chain and not the subunit-specific IL-6R and are therefore unresponsive to IL-6. However, EC are responsive to a combination of IL-6 and soluble IL-6R as measured by the activation of STATE, chemokine expression, and augmentation of ICAM-1. Activation by IL-6-IL-6R complexes was inhibited by an IL-6 receptor antagonist and potentiated by a superagonist. Hence, in vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment.