Sexual dimorphism in neutrophil function: Unveiling the discriminative nature of male and female neutrophils

IF 2.3 4区 医学 Q3 IMMUNOLOGY
Richard F. Kraus , Nina Doblinger , Michael A. Gruber , Maria S. Wagner , Johanna Rosenberger
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Abstract

Background

Women and men are different on many biological levels. Mounting evidence is now recognized that even the immune system has some significant sex differences, which are mainly cell mediated. This study investigated sex-specific differences in function and regulation of polymorphonuclear neutrophil granulocytes (PMNs) in male and female healthy human donors to gain a deeper understanding of the immune response and potential sex-specific dimorphism in immunology.

Methods

PMNs were obtained from whole blood samples of healthy female and male donors by leuko−/lymphospin density centrifugation. Chemotaxis assays using μ-slide chemotaxis chambers were performed, in which N-formylmethionin-leucyl-phenylalanine (fMLP) stimulated PMNs migrated through a type I collagen matrix. We measured the production of reactive oxygen species (ROS), the release of myeloperoxidase (MPO), and the formation of Neutrophil Extracellular Traps (NETs). Additionally, a flow cytometry assay was conducted to examine functional variations of neutrophil surface markers CD62L, CD11b, and CD66b, as well as the oxidative burst in PMNs obtained from male and female donors.

Results

Sex specific differences of neutrophil function could be determined. Male-derived PMNs initially migrated further distances, while female-derived PMNs showed more targeted movement. However, as the observation period progressed, male-derived PMNs began to exhibit more targeted migration, maintaining straightness towards the end. Differences in neutrophil surface marker expression were observed, with greater levels of CD11b and CD66b on male-derived PMNs after 2 h resting. The different immune effects between the sexes were seen in live cell imaging as well as in flow cytometry analyses.

Conclusion

The study revealed significant functional differences between PMNs from male and female donors. To gain reliable results in future PMN studies, it is crucial to consider the sex of the donor.
中性粒细胞功能的两性二态性:揭示男性和女性中性粒细胞的区别性。
背景:女性和男性在许多生理层面上是不同的。越来越多的证据表明,即使是免疫系统也存在一些显著的性别差异,这些差异主要是由细胞介导的。本研究调查了男性和女性健康人类供体中多形核中性粒细胞(PMNs)功能和调控的性别特异性差异,以深入了解免疫反应和免疫学中潜在的性别特异性二态性。方法:采用白细胞/淋巴磷脂密度离心法从健康男女献血者全血中提取pmn。采用μ玻片趋化室进行趋化实验,n-甲酰基蛋氨酸-亮氨酸-苯丙氨酸(fMLP)刺激pmn通过I型胶原基质迁移。我们测量了活性氧(ROS)的产生、髓过氧化物酶(MPO)的释放和中性粒细胞胞外陷阱(NETs)的形成。此外,流式细胞术检测中性粒细胞表面标记物CD62L、CD11b和CD66b的功能变化,以及从男性和女性供者获得的pmn中的氧化破裂。结果:可以确定中性粒细胞功能的性别特异性差异。雄性衍生的pmn最初迁移距离更远,而雌性衍生的pmn则表现出更有针对性的移动。然而,随着观察期的进展,雄性衍生的pmn开始表现出更有针对性的迁移,一直保持笔直。观察到中性粒细胞表面标记物表达的差异,休息2小时后,雄性来源的PMNs上CD11b和CD66b的水平更高。在活细胞成像和流式细胞术分析中可以看到两性之间不同的免疫效应。结论:研究显示男性和女性供体pmn在功能上存在显著差异。为了在未来的PMN研究中获得可靠的结果,考虑捐赠者的性别是至关重要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Immunobiology
Immunobiology 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
108
审稿时长
55 days
期刊介绍: Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.
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