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甘丙肽可调节人源和鼠源嗜中性粒细胞体外激活。

Galanin modulates human and murine neutrophil activation in vitro.

机构信息

Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.

出版信息

Acta Physiol (Oxf). 2015 Mar;213(3):595-602. doi: 10.1111/apha.12444. Epub 2015 Jan 7.

Abstract

AIMS

Polymorphonuclear neutrophils are key players in innate immunity. The innate immune system needs to be tightly controlled to ensure proper activation but also no overactivation. Galanin has been shown to regulate inflammatory reactions, and therefore, we aimed to elucidate the expression of galanin and its three receptors (GAL1 -GAL3 ) in polymorphonuclear neutrophils and to evaluate whether galanin exerts direct or indirect effects on human and murine polymorphonuclear neutrophils.

METHODS

Human peripheral polymorphonuclear neutrophils were isolated from fresh blood of healthy donors, and murine polymorphonuclear neutrophils were isolated from bone marrow of C57BL/6N mice. Gene expression was evaluated by qRT-PCR. As a marker for polymorphonuclear neutrophil activation, CD11b integrin surface expression was measured by FACS analysis. Furthermore, a label-free technology measuring ligand-induced dynamic mass redistribution was used to evaluate the response of polymorphonuclear neutrophils to galanin.

RESULTS

GAL2 receptor expression was found in both human and murine polymorphonuclear neutrophils, galanin and GAL3 receptor were exclusively expressed in murine bone marrow polymorphonuclear neutrophils, and GAL1 receptor was not detectable in polymorphonuclear neutrophils of either species. Galanin treatment was not able to induce CD11b integrin surface expression or dynamic mass redistribution in human polymorphonuclear neutrophils and murine bone marrow polymorphonuclear neutrophils. However, galanin treatment significantly enhanced the response of polymorphonuclear neutrophils of both species to interleukin-8.

CONCLUSION

Galanin can be regarded as an immunomodulatory peptide as it can sensitize polymorphonuclear neutrophils towards pro-inflammatory cytokines in humans and mice.

摘要

目的

多形核粒细胞是先天免疫系统的关键参与者。先天免疫系统需要受到严格控制,以确保适当的激活,但又不发生过度激活。神经肽 Y 已被证明可调节炎症反应,因此,我们旨在阐明神经肽 Y 及其三种受体(GAL1-GAL3)在多形核粒细胞中的表达,并评估神经肽 Y 是否对人源和鼠源多形核粒细胞发挥直接或间接作用。

方法

从健康供体的新鲜血液中分离人外周血多形核粒细胞,从 C57BL/6N 小鼠的骨髓中分离鼠源多形核粒细胞。通过 qRT-PCR 评估基因表达。作为多形核粒细胞活化的标志物,通过 FACS 分析测量 CD11b 整合素表面表达。此外,使用无标记技术测量配体诱导的动态质量重分布,以评估多形核粒细胞对神经肽 Y 的反应。

结果

在人源和鼠源多形核粒细胞中均发现 GAL2 受体表达,神经肽 Y 和 GAL3 受体仅在鼠源骨髓多形核粒细胞中表达,而 GAL1 受体在两种细胞类型的多形核粒细胞中均不可检测。神经肽 Y 处理不能诱导人源多形核粒细胞和鼠源骨髓多形核粒细胞的 CD11b 整合素表面表达或动态质量重分布。然而,神经肽 Y 处理显著增强了两种细胞类型的多形核粒细胞对白细胞介素-8 的反应。

结论

神经肽 Y 可被视为一种免疫调节肽,因为它可以使人源和鼠源多形核粒细胞对促炎细胞因子变得敏感。

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