首页> 外文期刊>Life sciences >Neutrophil effector functions triggered by Fc-gamma and/or complement receptors are dependent on B-ring hydroxylation pattern and physicochemical properties of flavonols.
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Neutrophil effector functions triggered by Fc-gamma and/or complement receptors are dependent on B-ring hydroxylation pattern and physicochemical properties of flavonols.

机译:Fc-γ和/或补体受体触发的嗜中性粒细胞效应子功能取决于B环羟化模式和黄酮醇的理化性质。

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摘要

Tissue damage in autoimmune diseases involves excessive production of reactive oxygen species (ROS) triggered by immune complexes (IC) and neutrophil (PMN) interactions via receptors for the Fc portion of IgG (FcgammaR) and complement receptors (CR). Modulation of both the effector potential of these receptors and ROS generation may be relevant to the maintenance of body homeostasis. In the present study, the modulatory effect of four flavonols (myricetin, quercetin, kaempferol, galangin) on rabbit PMN oxidative metabolism, specifically stimulated via FcgammaR, CR or both classes of receptors, was evaluated by luminol- and lucigenin-dependent chemiluminescence assays. Results showed that flavonol inhibitory effect was not dependent on the cell membrane receptor class stimulated but related to the lipophilicity of the compounds (their apparent partition coefficient values were obtained by high-performance liquid chromatography), and was also inversely related to the number of hydroxyl groups in the flavonol B ring and the ROS-scavenger activity (assessed by the luminol--H2O2--horseradish peroxidase reaction). Under the experimental conditions the flavonols tested were not toxic to PMNs (evaluated by lactate dehydrogenase release and trypan blue exclusion) and did not interfere with IC-induced phagocytosis (evaluated by transmission electron microscopy). Our results suggested that inhibition of IC-stimulated PMNs effector functions by the flavonols tested herein was the result of cooperation of different cellular mechanisms.
机译:自身免疫性疾病中的组织损伤涉及免疫复合物(IC)和嗜中性粒细胞(PMN)相互作用通过IgG Fc部分的受体(FcgammaR)和补体受体(CR)触发而过量产生活性氧(ROS)。这些受体的效应子电位和ROS产生的调节可能与体内稳态的维持有关。在本研究中,通过鲁米诺和依赖于荧光素的化学发光试验评估了四种黄酮醇(杨梅素,槲皮素,山emp酚,高良姜精)对兔PMN氧化代谢的调节作用,特别是通过FcgammaR,CR或两种受体刺激。结果表明,黄酮醇的抑制作用与所刺激的细胞膜受体类别无关,而与化合物的亲脂性有关(它们的表观分配系数值是通过高效液相色谱法获得的),并且与羟基数成反比。黄酮醇B环中的基团和ROS清除剂活性(通过鲁米诺-H2O2-辣根过氧化物酶反应评估)。在实验条件下,所测试的黄酮醇对PMN无毒(通过乳酸脱氢酶释放和锥虫蓝排除法评估),并且不干扰IC诱导的吞噬作用(通过透射电子显微镜评估)。我们的结果表明,本文测试的黄酮类化合物对IC刺激的PMNs效应子功能的抑制是不同细胞机制协同作用的结果。

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