Responsiveness of human neutrophils to interleukin-4: Induction of cytoskeletal rearrangements, de novo protein synthesis and delay of apoptosis
Responsiveness of human neutrophils to interleukin-4: Induction of cytoskeletal rearrangements, de novo protein synthesis and delay of apoptosis
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DOI：
10.1042/bj3250147
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发表时间：
1997-07-01
影响因子：
4.1
通讯作者：
Beaulieu, AD
中科院分区：
文献类型：
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作者：
Girard, D;Paquin, R;Beaulieu, AD
白介素 4 (IL-4) 和 IL-13 是具有许多共同生物活性的细胞因子。我们之前已经证明 IL-13 影响许多中性粒细胞反应，在这里我们将我们的观察扩展到 IL-4。我们首次提出人类中性粒细胞上存在功能性 IL-4 受体的直接证据。我们报告说，IL-4 以浓度依赖性方式诱导 RNA 合成，并且基于对细胞形态变化和铺展到玻璃上的诱导的观察，我们证明 IL-4 激活中性粒细胞细胞骨架重排。我们进一步表明，IL-4 是中性粒细胞中蛋白质从头合成的有效激活剂，并且我们通过微测序将其中一种蛋白质鉴定为细胞骨架蛋白肌动蛋白。我们还首次证明肌动蛋白在中性粒细胞中被切割成至少两个类似于 30 kDa (pI 5.4) 和类似于 25 kDa (pI 5.0) 的片段。最后，我们报告了 IL-4 延迟了中性粒细胞凋亡，这是通过细胞离心制剂的形态学观察以及通过使用碘化丙啶和 Hoechst 试剂的流式细胞术测量染色差异来评估的。综上所述，我们得出结论，IL-4 是一种比之前认为的更有效的中性粒细胞激动剂。我们讨论了IL-4诱导肌动蛋白新合成与该细胞因子延迟细胞凋亡的机制有关的可能性；此外，该蛋白质的裂解可能有助于细胞凋亡过程。
Interleukin-4 (IL-4) and IL-13 are cytokines that share many biological activities. We have previously demonstrated that IL-13 affects a number of neutrophil responses, and here we extend our observations to IL-4. We present, for the first time, direct evidence for the presence of functional IL-4 receptors on human neutrophils. We report that IL-4 induces RNA synthesis in a concentration-dependent manner and, based on observations of the induction of morphological cell shape changes and spreading onto glass, we demonstrate that IL-4 activates neutrophil cytoskeletal rearrangements. We further show that IL-4 is a potent activator of de novo protein synthesis in neutrophils, and we identify by microsequencing one of these proteins as the cytoskeletal protein actin. We were also able to demonstrate for the first time that actin is cleaved into at least two fragments of similar to 30 kDa (pI 5.4) and similar to 25 kDa (pI 5.0) in neutrophils. Finally, we report that IL-4 delays neutrophil apoptosis, as assessed by morphological observations from cytocentrifuge preparations, as well as by measurement of differences in staining by flow cytometry with both propidium iodide and Hoechst reagent. Taken together, we conclude that IL-4 is a more potent neutrophil agonist than previously believed. We discuss the possibility that the induction of the de nova synthesis of actin by IL-4 is related to the mechanism by which this cytokine delays apoptosis; in addition, the cleavage of this protein is likely to contribute to the apoptotic process.