Endotoxin promotes neutrophil hierarchical chemotaxis via the p38-membrane receptor pathway.
Endotoxin promotes neutrophil hierarchical chemotaxis via the p38-membrane receptor pathway.
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内毒素通过 p38 膜受体途径促进中性粒细胞分级趋化性
DOI：
10.18632/oncotarget.12093
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发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Sun B
中科院分区：
文献类型：
--
作者：
Wang X;Qin W;Zhang Y;Zhang H;Sun B
中性粒细胞是外周血中最丰富的白细胞，在细菌感染、肿瘤免疫和创伤修复中起关键作用。澄清中性粒细胞趋化性的免疫活性的目标网站的过程中一直是一个焦点，在过去的十年中增加的兴趣。在细菌感染灶中，中性粒细胞向细菌衍生的化学引诱物N-甲酰基-Met-Leu-Phe（fMLP）迁移，而忽略其他中间化学引诱物到达感染区域。使用琼脂糖下的趋化性测定，我们观察到细菌fMLP诱导的中性粒细胞趋化信号覆盖白细胞介素8（IL-8）和白三烯B4（LTB 4）诱导的趋化信号。此外，在细菌脂多糖（LPS）的存在下，fMLP诱导的分级趋化信号增强。进一步的研究表明，LPS增加了fMLP受体，甲酰肽受体1（FPR 1）的膜表达。然而，IL-8和LTB 4的膜受体的表达水平被LPS施用降低。人磷酸化丝裂原活化蛋白激酶（MAPK）蛋白质组阵列显示，p38通路被LPS刺激显着激活。此外，p38负责中性粒细胞膜趋化因子受体的表达改变。抑制中性粒细胞p38恢复LPS改善的分级趋化性。总之，这些数据表明，内毒素通过p38-膜受体途径促进中性粒细胞分级趋化。
Neutrophils are the most abundant leukocytes in peripheral blood and play critical a role in bacterial infection, tumor immunity and wound repair. Clarifying the process of neutrophil chemotaxis to target sites of immune activity has been a focus of increased interest within the past decade. In bacterial infectious foci, neutrophils migrate toward the bacterial-derived chemoattractant N-formyl-Met-Leu-Phe (fMLP) and ignore other intermediary chemoattractants to arrive at the area of infection. Using an under agarose chemotaxis assay, we observed that the bacterial fMLP-induced neutrophil chemotaxis signal overrode interleukin 8 (IL-8)- and leukotriene B4 (LTB4)-induced chemotaxis signals. Moreover, in the presence of bacterial lipopolysaccharide (LPS), the fMLP-induced hierarchical chemotaxis signal was enhanced. Further studies revealed that LPS increased the membrane expression of the fMLP receptor, formyl peptide receptor 1 (FPR1). However, expression levels of the membrane receptors for IL-8 and LTB4 were decreased by LPS administration. A human Phospho-mitogen-activated protein kinase (MAPK) proteome array showed that the p38 pathway was significantly activated by LPS stimulation. Moreover, p38 was responsible for the altered expression of neutrophil membrane chemoattractant receptors. Inhibition of neutrophil p38 restored LPS-improved hierarchical chemotaxis. Taken together, these data indicate that endotoxin promotes neutrophil hierarchical chemotaxis via the p38-membrane receptor pathway.