Bociąga-Jasik Monika, Góralska Joanna, Polus Anna, Śliwa Agnieszka, Gruca Anna, Raźny Urszula, Zdzienicka Anna, Garlicki Aleksander, Mach Tomasz, Dembińska-Kieć Aldona
Chair of Gastroenterology, Hepatology and Infectious Diseases, Department of Infectious Diseases Jagiellonian University, Collegium Medicum, Sniadeckich 5, 31-531 Kraków, Poland.
Curr HIV Res. 2013 Jun;11(4):263-70. doi: 10.2174/1570162x113116660055.
HIV infection results in the development of immunodeficiency mainly due to the apoptosis of infected and by stander CD4 cells. The aim of the study was to follow the mitochondrial dependent pathway of apoptosis, one of the suggested mechanisms of above process. The inner mitochondrial membrane potential (MMP), Adenosine-5'-triphosphate (ATP) generation, apoptosis and necrosis markers of peripheral mononuclear cells (PBMCs) were compared in HIV infected patients and HIV negative control group. The correlation of blood viral load, TNFα concentration, CD4 cells count and duration of ARV therapy was considered. Additionally, group of HIV infected ARV-naive patients was involved for the follow-up study and the effects of one year of ARV therapy on measured parameters were studied. PBMCs of HIV infected individuals (especially without ARV therapy) demonstrated lower MMP and ATP generation and higher percentage of apoptotic/necrotic PBMCs. Correlation between blood TNFα level and mitochondrial dysfunction was observed. The first months of ARV therapy resulted in most significant restoration of mitochondrial function and living PBMCs count. HIV infection and ARV therapy have significant impact on mitochondrial function and apoptosis of PBMCs. They are driven by abnormal mitochondrial function apoptosis of immune cells which seems to be the key element leading to immunosuppression, thus an early intervention in this process by therapy can be beneficial for symptomatology of HIV infected patients.
HIV感染主要由于受感染的CD4细胞和旁观CD4细胞的凋亡导致免疫缺陷的发展。本研究的目的是追踪凋亡的线粒体依赖性途径,这是上述过程的一种推测机制。比较了HIV感染患者和HIV阴性对照组外周血单个核细胞(PBMC)的线粒体内膜电位(MMP)、三磷酸腺苷(ATP)生成、凋亡和坏死标志物。考虑了血液病毒载量、TNFα浓度、CD4细胞计数与抗逆转录病毒治疗持续时间之间的相关性。此外,纳入了未接受抗逆转录病毒治疗的HIV感染患者组进行随访研究,并研究了一年抗逆转录病毒治疗对测量参数的影响。HIV感染者(尤其是未接受抗逆转录病毒治疗者)的PBMC表现出较低的MMP和ATP生成,以及较高百分比的凋亡/坏死PBMC。观察到血液TNFα水平与线粒体功能障碍之间的相关性。抗逆转录病毒治疗的最初几个月导致线粒体功能和存活PBMC计数最显著的恢复。HIV感染和抗逆转录病毒治疗对PBMC的线粒体功能和凋亡有显著影响。它们是由免疫细胞异常的线粒体功能凋亡驱动的,这似乎是导致免疫抑制的关键因素,因此在此过程中通过治疗进行早期干预可能对HIV感染患者的症状有益。