Caini P, Guerra C Tosti, Giannini C, Giannelli F, Gragnani L, Petrarca A, Solazzo V, Monti M, Laffi G, Zignego A L
Department of Internal Medicine, Center for the Study of Systemic Manifestations of Hepatitis Viruses MASVE and Higher Education Research and Transfer Center DENOTHE, University of Florence, Florence, Italy.
J Viral Hepat. 2007 Jan;14(1):22-8. doi: 10.1111/j.1365-2893.2006.00766.x.
Hepatitis C virus (HCV) chronically infects about 200 million individuals worldwide and leads to severe liver and lymphatic diseases. HCV circulates in the serum, associated with apoB-containing lipoproteins. Platelet-activating factor (PAF), a pro-inflammatory mediator, is mainly modulated by plasma PAF-acetylhydrolase (pPAF-AH), associated with ApoB100-containing low-density lipoproteins (LDL). The aim of the study was to evaluate the potential effects of chronic HCV infection on the PAF/pPAF-AH system. HCV-RNA was detected in plasma, peripheral blood mononuclear cells (PBMC) and liver samples. Plasma PAF levels, pPAF-AH activity, ApoB100 serum titres and pPAF-AH mRNA levels in cultured macrophages were determined. Plasma PAF levels were significantly higher and pPAF-AH activity was significantly lower in HCV patients than in controls. No significant modifications of pPAF-AH mRNA in macrophages or in ApoB100 values were observed in HCV patients compared with controls. Patients who cleared HCV after antiviral treatment showed a complete restoration of pPAF-AH activity and significant decrease of PAF levels during the follow-up. No data exist about the PAF/pPAF-AH system behaviour during HCV infection. This study shows that in HCV patients modifications of pPAF-AH activity/PAF levels take place and that HCV clearance restored pPAF-AH activity. This suggests that circulating viral particles play a role in PAF/pPAF-AH system modifications and such an alteration could be involved in HCV-related damage.
丙型肝炎病毒(HCV)在全球约2亿人中长期感染,并导致严重的肝脏和淋巴疾病。HCV在血清中循环,与含载脂蛋白B的脂蛋白相关。血小板活化因子(PAF)是一种促炎介质,主要由血浆PAF-乙酰水解酶(pPAF-AH)调节,pPAF-AH与含载脂蛋白B100的低密度脂蛋白(LDL)相关。本研究的目的是评估慢性HCV感染对PAF/pPAF-AH系统的潜在影响。在血浆、外周血单核细胞(PBMC)和肝脏样本中检测到HCV-RNA。测定了培养巨噬细胞中的血浆PAF水平、pPAF-AH活性、载脂蛋白B100血清滴度和pPAF-AH mRNA水平。HCV患者的血浆PAF水平显著高于对照组,而pPAF-AH活性显著低于对照组。与对照组相比,未观察到HCV患者巨噬细胞中pPAF-AH mRNA或载脂蛋白B100值有明显变化。抗病毒治疗后清除HCV的患者在随访期间显示pPAF-AH活性完全恢复,PAF水平显著降低。关于HCV感染期间PAF/pPAF-AH系统的行为尚无数据。本研究表明,HCV患者中发生了pPAF-AH活性/PAF水平的改变,并且HCV清除可恢复pPAF-AH活性。这表明循环病毒颗粒在PAF/pPAF-AH系统改变中起作用,这种改变可能与HCV相关损伤有关。