Kiebala Michelle, Singh Meera V, Piepenbrink Michael S, Qiu Xing, Kobie James J, Maggirwar Sanjay B
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
Division of Infectious Diseases, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
PLoS One. 2015 Jun 15;10(6):e0130061. doi: 10.1371/journal.pone.0130061. eCollection 2015.
Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV) infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB) inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK) activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders.
近期研究表明，血小板作为无核血细胞，在炎症性疾病中发挥着重要作用。重要的是，血小板还可能导致各种与1型人类免疫缺陷病毒（HIV）感染相关的炎症性继发疾病，包括神经功能障碍和心血管并发症。事实上，HIV感染常与血小板激活剂水平升高有关。此外，可卡因是HIV感染者常用的一种滥用药物，可导致人体血小板激活增加。鉴于精心编排的信号机制对血小板激活至关重要，且核因子-κB（NF-κB）抑制剂可改变血小板功能，因此HIV感染期间NF-κB信号在血小板激活中的作用值得进一步研究。在此，我们检验了以下假设：抑制性κB激酶复合体（IKK）激活是HIV和可卡因诱导血小板激活的关键因素。利用HIV阳性和HIV阴性个体的全血，无论是否有可卡因滥用情况，通过流式细胞术评估血小板激活，同时通过免疫印迹和体外激酶测定分析IKK激活情况。我们发现，以CD62P表达衡量，HIV患者血小板激活增加与报告的可卡因使用情况无关。此外，可卡因和HIV在体外处理全血时不会激活血小板。最后，HIV诱导的血小板激活不涉及NF-κB信号中间体IKKβ。HIV患者的血小板激活不受可卡因滥用的影响。这些结果支持这样一种观点，即非IKK靶向方法将更适合治疗与HIV相关的炎症性疾病。
