Oliveira S H P, Canetti C, Ribeiro R A, Cunha F Q
Department of Basic Science, School of Dentistry, Sao Paulo State University, Araçatuba, Sao Paulo, Brazil.
Inflammation. 2008 Feb;31(1):36-46. doi: 10.1007/s10753-007-9047-x.
In the present study, we investigate whether mast cells and macrophages are involved in the control of IL-1beta-induced neutrophil migration, as well as the participation of chemotactic mediators. IL-1beta induced a dose-dependent neutrophil migration to the peritoneal cavity of rats which depends on LTB(4), PAF and cytokines, since the animal treatment with inhibitors of these mediators (MK 886, PCA 4248 and dexamethasone respectively) inhibited IL-1beta-induced neutrophil migration. The neutrophil migration induced by IL-1beta 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-1beta released a neutrophil chemotactic factor, which mimicked the neutrophil migration induced by IL-1beta. The chemotactic activity of the supernatant of IL-1beta-stimulated macrophages is due to the presence of LTB(4), since MK 886 inhibited its release. Moreover, the chemotactic activity of IL-1beta-stimulated mast cells supernatant is due to the presence of IL-1beta 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-1beta depends upon LTB(4) released by macrophages and upon IL-1beta and TNFalpha released by mast cells.
在本研究中，我们探究肥大细胞和巨噬细胞是否参与白细胞介素-1β（IL-1β）诱导的中性粒细胞迁移的调控，以及趋化介质的参与情况。IL-1β诱导大鼠腹腔出现剂量依赖性的中性粒细胞迁移，这一迁移依赖于白三烯B4（LTB4）、血小板活化因子（PAF）和细胞因子，因为用这些介质的抑制剂（分别为MK 886、PCA 4248和地塞米松）处理动物可抑制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，因为肥大细胞的耗竭会减少这一过程，而巨噬细胞数量的增加则会增强迁移。此外，用IL-1β刺激肥大细胞或巨噬细胞会释放一种中性粒细胞趋化因子，该因子可模拟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归因于LTB4的存在，因为MK 886可抑制其释放。此外，IL-1β刺激的肥大细胞上清液的趋化活性归因于IL-1β和肿瘤坏死因子-α（TNF-α）的存在，因为针对这些细胞因子的抗体可抑制其活性。此外，在上清液中检测到了大量这些细胞因子。总之，我们的结果表明，IL-1β诱导的中性粒细胞迁移取决于巨噬细胞释放的LTB4以及肥大细胞释放的IL-1β和TNF-α。
