Departamento de Análises Clínicas, Toxicológicas e Bromatológicas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Harvard Glycomics Center, Harvard Medical School, Boston, MA, USA.
Methods Mol Biol. 2022;2442:549-564. doi: 10.1007/978-1-0716-2055-7_29.
Reactive oxygen species (ROS) have been extensively studied in biology in the past years. This class of molecules can be derived from endogenous sources (e.g., phagocytic cells as neutrophils, eosinophils, monocytes, macrophages, and organelles as mitochondria and peroxisomes) and participate in physiological and pathological conditions. The beneficial and harmful effects of ROS depend on redox regulation, which establishes the balance between their production and the activity of antioxidant systems to prevent oxidative stress in vivo. Neutrophils are the immune effectors most well depicted with an intense oxidative burst in response to tissue inflammation. Several proteins and members of the galectin family are involved in this fine modulation of ROS production by neutrophils. Interestingly, studies have indicated that Galectin-1 (Gal-1) can up- or downregulate ROS production by neutrophils even when exposed to N-formyl-Met-Leu-Phe (fMLP) or Phorbol Myristate Acetate (PMA), both of which are potent neutrophil stimulants that trigger high levels of ROS production. Similarly, Galectin-3 (Gal-3) induces ROS in neutrophils from a sterile or nonsterile inflammatory environment, possibly creating a negative loop that could control ROS production. Besides, superoxide production is also induced by Galectin-8 (Gal-8) and Galectin-9 (Gal-9) in neutrophils but in a different manner. We describe herein the luminol and lucigenin-dependent chemiluminescence technique by using a luminometer as a method of assessment to measure ROS production by human neutrophils isolated and exposed to purified human recombinant Gal-1. The protocol described herein could be applied for the investigation of the role of other galectins in the modulation of ROS production by neutrophils.
活性氧 (ROS) 在过去几年的生物学研究中得到了广泛的研究。这类分子可以来源于内源性来源(例如吞噬细胞如中性粒细胞、嗜酸性粒细胞、单核细胞、巨噬细胞和细胞器如线粒体和过氧化物酶体),并参与生理和病理条件。ROS 的有益和有害影响取决于氧化还原调节,它在其产生和抗氧化系统的活性之间建立了平衡,以防止体内氧化应激。中性粒细胞是免疫效应物,在对组织炎症的反应中表现出强烈的氧化爆发。几种蛋白质和半乳糖凝集素家族的成员参与了中性粒细胞 ROS 产生的这种精细调节。有趣的是,研究表明半乳糖凝集素-1(Gal-1)即使在暴露于 N-甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸(fMLP)或佛波醇 12,13-二丁酸酯(PMA)时,也可以上调或下调中性粒细胞的 ROS 产生,这两种物质都是强烈的中性粒细胞刺激物,可引发高水平的 ROS 产生。同样,半乳糖凝集素-3(Gal-3)在来自无菌或非无菌炎症环境的中性粒细胞中诱导 ROS,可能形成一个负反馈环,从而控制 ROS 的产生。此外,半乳糖凝集素-8(Gal-8)和半乳糖凝集素-9(Gal-9)也以不同的方式诱导中性粒细胞中超氧化物的产生。本文描述了使用发光计作为评估方法的鲁米诺和光解素依赖性化学发光技术,以测量分离并暴露于纯化的人重组 Gal-1 的人中性粒细胞中的 ROS 产生。本文描述的方案可用于研究其他半乳糖凝集素在调节中性粒细胞 ROS 产生中的作用。