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活化单核细胞表型特征支持R5嗜性人类免疫缺陷病毒

Characteristics of Activated Monocyte Phenotype Support R5-Tropic Human Immunodeficiency Virus.

作者信息

Munsaka Sody M, Agsalda Melissa, Troelstrup David, Hu Ningjie, Yu Qigui, Shiramizu Bruce

机构信息

Hawaii AIDS Clinical Research Program, Department of Medicine, John A Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.

出版信息

Immunol Immunogenet Insights. 2009;1:15-20. doi: 10.4137/iii.s2011.

Abstract

BACKGROUND

Microbial translocation has been recognized as an important factor in monocyte activation and contributing to AIDS pathogenesis with elevated plasma lipopolysaccharide (LPS) levels, as a marker for microbial translocation, seen in advanced HIV disease. Therefore, the current study was undertaken to assess monocyte activation in vitro by LPS and to determine its impact on monocyte phenotype. METHODS: Monocytes from non-HIV-infected donors were analyzed for CD14, CD16, CD69, TNFα, and CCR5 by flow cytometry pre- and post-stimulation with LPS. In-vitro cultures were then set up to expose non-activated and activated monocytes to R5-, X4-, and dual (R5/X4)-tropic viruses; and the amount of HIV present on the cells was assayed. RESULTS: Non-HIV-infected monocytes, after LPS stimulation, were confirmed to have an activated phenotype with increase in CD16 and CD69 surface expressions (p<0.05). The activation phenotype was supported by increase in TNFα production, p<0.05. The activated monocytes had increased surface CCR5 (from 21% to 98%; p=0.05); and were found to have more R5-tropic virus than non-activated monocytes (p<0.05). CONCLUSIONS: Following activation by LPS, non-HIV-infected monocytes were found to have increase in surface CCR5. These activated monocytes, when exposed to R5-tropic virus, were found to have more virus compared to non-activated monocytes. The significance of the findings could lie in explaining how microbial translocation plays a role in HIV progression; and possibly promoting CCR5-directed strategies in treating HIV.

摘要

背景

微生物易位已被认为是单核细胞活化的一个重要因素,并通过血浆脂多糖(LPS)水平升高促进艾滋病发病机制,血浆LPS水平作为微生物易位的标志物,在晚期HIV疾病中可见。因此,本研究旨在评估LPS体外诱导的单核细胞活化情况,并确定其对单核细胞表型的影响。方法:采用流式细胞术分析来自未感染HIV供体的单核细胞在LPS刺激前后的CD14、CD16、CD69、TNFα和CCR5表达。随后建立体外培养体系,将未活化和活化的单核细胞暴露于R5嗜性、X4嗜性和双嗜性(R5/X4)病毒中,并检测细胞上的HIV含量。结果:未感染HIV的单核细胞在LPS刺激后,CD16和CD69表面表达增加,证实具有活化表型(p<0.05)。TNFα产生增加也支持了活化表型(p<0.05)。活化的单核细胞表面CCR5增加(从21%增至98%;p=0.05);并且发现其比未活化的单核细胞含有更多的R5嗜性病毒(p<0.05)。结论:LPS激活后,未感染HIV的单核细胞表面CCR5增加。这些活化的单核细胞在暴露于R5嗜性病毒时,与未活化的单核细胞相比,含有更多的病毒。这些发现的意义可能在于解释微生物易位如何在HIV进展中发挥作用;并可能推动针对CCR5的HIV治疗策略。

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