Increased responsiveness of murine eosinophils to MIP‐1β (CCL4) and TCA‐3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8
Increased responsiveness of murine eosinophils to MIP‐1β (CCL4) and TCA‐3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8
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小鼠嗜酸性粒细胞对 MIP-1β (CCL4) 和 TCA-3 (CCL1) 的反应性增强是由其特定受体 CCR5 和 CCR8 介导的
DOI：
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发表时间：
2002
影响因子：
5.5
通讯作者：
N. Lukacs
中科院分区：
文献类型：
--
作者：
S. Oliveira;S. Lira;C. Martínez;M. Wiekowski;L. Sullivan;N. Lukacs
在本研究中，我们研究了趋化因子介导的反应和受体表达对小鼠嗜酸性粒细胞的调节。MIP-1α（CCL 3）和嗜酸性粒细胞趋化因子（CCL 11）在抗原诱导的嗜酸性粒细胞和外周血嗜酸性粒细胞中诱导了显着且仅部分重叠的细胞内钙通量，而MCP-1（CCL 2）、MDC（CCL 22）、MIP-1β（CCL 4）和TCA-3（CCL 1）则没有。为了证明特异性受体的功能用途，我们检查了趋化反应。外周血嗜酸性粒细胞向MIP-1α（CCL 3）和嗜酸性粒细胞活化趋化因子（CCL 11）迁移，但不向MCP-1（CCL 2）、MDC（CCL 22）、MIP-1β（CCL 4）和TCA-3（CCL 1）迁移。抗原诱导的嗜酸性粒细胞向MIP-1α（CCL 3）和嗜酸性粒细胞趋化因子（CCL 11）迁移，但也响应于MIP-1β（CCL 4）和TCA-3（CCL 1）而迁移，这表明抗原诱导的嗜酸性粒细胞上额外的趋化因子受体上调。额外趋化因子受体反应的上调似乎部分是由于细胞因子活化，因为TNF-α和/或IL-4能够上调嗜酸性粒细胞中CCR 1、-3、-5和-8 mRNA表达以及对适当配体的迁移反应。使用CCR 5和CCR 8特异性抗体，分别对MIP-1β和TCA-3的趋化反应显著降低。最后，这些新受体的表达似乎对活化和脱粒有影响，因为MIP-1β（CCL 4）和TCA-3（CCL 1）从激发的嗜酸性粒细胞诱导显著水平的LTC 4。这些结果表明，嗜酸性粒细胞可能在炎症、过敏反应进展过程中上调并使用额外的趋化因子受体进行迁移和活化。
In the present study, we investigated the regulation of chemokine‐mediated responses and receptor expression on eosinophils from mice. MIP‐1α (CCL3) and eotaxin (CCL11) induced a significant and only partially overlapping intracellular calcium flux in antigen‐elicited and peripheral blood eosinophils, and MCP‐1 (CCL2), MDC (CCL22), MIP‐1β (CCL4), and TCA‐3 (CCL1) did not. To demonstrate functional use of the specific receptors, we examined chemotactic responses. Peripheral blood eosinophils migrated toward MIP‐1α (CCL3) and eotaxin (CCL11) but not MCP‐1 (CCL2), MDC (CCL22), MIP‐1β (CCL4), and TCA‐3 (CCL1). Antigen‐elicited eosinophils migrated toward MIP‐1α (CCL3) and eotaxin (CCL11), but also migrated in response to MIP‐1β (CCL4) and TCA‐3 (CCL1), suggesting the up‐regulation of additional chemokine receptors on antigen‐elicited eosinophils. The up‐regulation of the additional chemokine‐receptor responses appeared to be in part because of cytokine activation, because TNF‐α and/or IL‐4 were able to up‐regulate CCR1, ‐3, ‐5, and ‐8 mRNA expression in eosinophils as well as migration responses to the appropriate ligands. Using antibodies specific for CCR5 and CCR8, the chemotactic response to MIP‐1β and TCA‐3, respectively, was reduced significantly. Finally, the expression of these new receptors appears to have an effect on activation and degranulation because MIP‐1β (CCL4) and TCA‐3 (CCL1) induce significant levels of LTC4 from elicited eosinophils. These results suggest that eosinophils may up‐regulate and use additional chemokine receptors during progression of inflammatory, allergic responses for migration and activation.
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DOI：
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发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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DOI：
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发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Beck,LA;Dalke,S;Leiferman,KM;Bickel,CA;Hamilton,R;Rosen,H;Bochner,BS;Schleimer,RP
通讯作者：
Schleimer,RP