Differential regulation of neutrophil chemotaxis to IL-8 and fMLP by GM-CSF: lack of direct effect of oestradiol
Differential regulation of neutrophil chemotaxis to IL-8 and fMLP by GM-CSF: lack of direct effect of oestradiol
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DOI：
10.1111/j.1365-2567.2005.02280.x
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发表时间：
2006-02-01
期刊：
影响因子：
6.4
通讯作者：
Fanger, MW
中科院分区：
文献类型：
--
作者：
Shen, L;Smith, JM;Fanger, MW
中性粒细胞是女性生殖道的正常组成部分，其数量在月经前月经周期的分泌后期增加。雌性生殖道组织中产生几种细胞因子。特别是粒细胞-巨噬细胞集落刺激因子（GM-CSF），一种有效的中性粒细胞激活剂，由女性生殖道上皮细胞以高浓度分泌。我们先前观察到GM-CSF与白细胞介素-8（IL-8）在增强中性粒细胞的趋化性方面具有强烈的协同作用。因此，我们研究了在没有GM-CSF的情况下，用GM-CSF预处理中性粒细胞是否会引发随后对IL-8的趋化性。令人惊讶的是，GM-CSF的3小时脉冲严重降低了对IL-8的趋化性，而N-甲酰基-甲基-亮氨酰基-苯丙氨酸（fMLP）介导的趋化性得以保留。相反，当细胞在没有GM-CSF的情况下孵育时，它们保留了IL-8介导的迁移，但失去了fMLP趋化性。趋化性的这些变化与CXCR 1、CXCR 2或甲酰肽受体的表达无关。然而，IL-8介导的p44/42丝裂原活化蛋白激酶的磷酸化在不再迁移到IL-8的中性粒细胞中大大减少，并且在不再迁移到fMLP的细胞中减少。雌二醇，这是一些报道发挥抗炎作用的中性粒细胞，并没有改变GM-CSF的影响。这些数据表明，中性粒细胞的功能可能会改变细胞因子，如GM-CSF通过调制信号和独立的表面受体的表达。
Neutrophils are a normal constituent of the female reproductive tract and their numbers increase in the late secretory phase of the menstrual cycle prior to menses. Several cytokines are produced in female reproductive tract tissue. In particular granulocyte-macrophage colony-stimulating factor (GM-CSF), a potent activator of neutrophils, is secreted in high concentrations by female reproductive tract epithelia. We previously observed that GM-CSF synergizes strongly with interleukin-8 (IL-8) in enhancing chemotaxis of neutrophils. Thus we investigated whether pretreatment of neutrophils with GM-CSF would prime subsequent chemotaxis to IL-8 in the absence of GM-CSF. Surprisingly, a 3-hr pulse of GM-CSF severely diminished chemotaxis to IL-8, whereas N-formyl-methyl-leucyl-phenylalanine (fMLP)-mediated chemotaxis was retained. Conversely, when cells were incubated without GM-CSF they retained IL-8-mediated migration but lost fMLP chemotaxis. These changes in chemotaxis did not correlate with expression of CXCR1, CXCR2 or formyl peptide receptor. However, IL-8-mediated phosphorylation of p44/42 mitogen-activated protein kinase was greatly reduced in neutrophils that no longer migrated to IL-8, and was diminished in cells that no longer migrated to fMLP. Oestradiol, which is reported by some to exert an anti-inflammatory effect on neutrophils, did not change the effects of GM-CSF. These data suggest that neutrophil function may be altered by cytokines such as GM-CSF through modulation of signalling and independently of surface receptor expression.