Neutrophil migration induced by IL-1β depends upon LTB4 released by macrophages and upon TNF-α and IL-1β released by mast cells

Neutrophil migration induced by IL-1β depends upon LTB4 released by macrophages and upon TNF-α and IL-1β released by mast cells
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DOI:
10.1007/s10753-007-9047-x
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发表时间:
2008-02-01
期刊:
影响因子:
5.1
通讯作者:
Cunha, F. Q.
Cunha, F. Q.
中科院分区:
医学2区
文献类型:
--
作者:
Oliveira, S. H. P.;Canetti, C.;Cunha, F. Q.

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在本研究中,我们研究肥大细胞和巨噬细胞是否参与了IL-1β诱导的中性粒细胞迁移的控制,以及趋化介质的参与。IL-1β可诱导中性粒细胞向大鼠腹膜腔内的迁移,这种作用依赖于LTB4、PAF和细胞因子,因为这些介质的抑制剂(分别为MK 886、PCA 4248和地塞米松)可抑制IL-1β诱导的中性粒细胞迁移。IL-1β诱导的中性粒细胞迁移依赖于肥大细胞和巨噬细胞,因为肥大细胞的耗尽减少了这一过程,而巨噬细胞数量的增加则促进了中性粒细胞的迁移。此外,在IL-1β刺激下,肥大细胞或巨噬细胞释放一种中性粒细胞趋化因子,该因子模仿IL-1β诱导的中性粒细胞迁移。IL-1β刺激的巨噬细胞上清液的趋化活性是由于LTB4的存在,因为MK 886抑制了它的释放。此外,IL-1β刺激的肥大细胞上清液的趋化活性是由于IL-1β和肿瘤坏死因子-α的存在,因为这些细胞因子的抗体抑制了其活性。此外,在上清液中检测到大量的这些细胞因子。综上所述,我们的结果表明,IL-1β诱导的中性粒细胞迁移依赖于巨噬细胞释放的LTB4和肥大细胞释放的IL-1β和TNFα。
In the present study, we investigate whether mast cells and macrophages are involved in the control of IL-1 beta-induced neutrophil migration, as well as the participation of chemotactic mediators. IL-1 beta induced a dose-dependent neutrophil migration to the peritoneal cavity of rats which depends on LTB4, PAF and cytokines, since the animal treatment with inhibitors of these mediators (MK 886, PCA 4248 and dexamethasone respectively) inhibited IL-1 beta-induced neutrophil migration. The neutrophil migration induced by IL-1 beta is dependent on mast cells and macrophages, since depletion of mast cells reduced the process whereas the increase of macrophage population enhanced the migration. Moreover, mast cells or macrophages stimulated with IL-1 beta released a neutrophil chemotactic factor, which mimicked the neutrophil migration induced by IL-1 beta. The chemotactic activity of the supernatant of IL-1 beta-stimulated macrophages is due to the presence of LTB4, since MK 886 inhibited its release. Moreover, the chemotactic activity of IL-1 beta-stimulated mast cells supernatant is due to the presence of IL-1 beta and TNF-alpha, since antibodies against these cytokines inhibited its activity. Furthermore, significant amounts of these cytokines were detected in the supernatant. In conclusion, our results suggest that neutrophil migration induced by IL-1 beta depends upon LTB4 released by macrophages and upon IL-1 beta and TNF alpha released by mast cells.