Holme P A, Müller F, Solum N O, Brosstad F, Frøland S S, Aukrust P
Research Institute for Internal Medicine, Medical Department A, The National Hospital, University of Oslo, Norway.
FASEB J. 1998 Jan;12(1):79-89. doi: 10.1096/fasebj.12.1.79.
Besides their role in hemostasis, platelets are involved in inflammatory and immunological processes, and we hypothesize that platelet activation may play an immunopathogenetic role in HIV-1 infection. Blood was drawn from 15 controls and 20 HIV-1-infected patients with normal platelet counts, classified into groups of non-AIDS and AIDS. Platelet activation was detected using flow cytometry with mAbs against the release markers P-selectin and CD63, mAb against GPIb, and the probe annexin V detecting surface exposure of aminophospholipids. The amount of microvesicles was measured using mAb against GPIIIa. Compared to controls, blood samples from HIV-1-infected patients showed significantly enhanced levels of microvesicles and activated platelets as detected by their exposure of P-selectin, CD63, and aminophospholipids, as well as reduction in GPIb expression. Increased expression of P-selectin and amounts of microvesicles were most pronounced in advanced clinical and immunological disease. When studying the effect of HIV-1 protease inhibitor therapy (indinavir) on platelet activation, we found that concomitant with a profound decrease in plasma viral load, there was a near normalization of several of the parameters reflecting enhanced platelet activation. Finally, we demonstrated that platelets may be an important source of the chemokine RANTES in HIV-1-infected patients. Although both unstimulated and SFLLRN-stimulated platelets from asymptomatic patients had enhanced release of RANTES, platelets from AIDS patients were characterized by markedly enhanced spontaneous, but decreased SFLLRN-stimulated release of this chemokine. Taken together, these results, which demonstrate for the first time increased platelet activation in HIV-1-infected patients with normal platelet counts, may represent a previously unrecognized immunopathogenic factor in HIV-1 infection.
除了在止血过程中发挥作用外，血小板还参与炎症和免疫过程，我们推测血小板活化可能在HIV-1感染中发挥免疫致病作用。从15名对照者和20名血小板计数正常的HIV-1感染患者中采集血液，这些患者分为非艾滋病组和艾滋病组。使用针对释放标志物P-选择素和CD63的单克隆抗体、针对糖蛋白Ib（GPIb）的单克隆抗体以及检测氨基磷脂表面暴露的膜联蛋白V探针，通过流式细胞术检测血小板活化情况。使用针对糖蛋白IIIa（GPIIIa）的单克隆抗体测量微泡的数量。与对照组相比，HIV-1感染患者的血液样本显示，通过P-选择素、CD63和氨基磷脂的暴露检测到微泡和活化血小板水平显著升高，同时GPIb表达降低。P-选择素表达增加和微泡数量增加在晚期临床和免疫疾病中最为明显。在研究HIV-1蛋白酶抑制剂疗法（茚地那韦）对血小板活化的影响时，我们发现，随着血浆病毒载量的大幅下降，反映血小板活化增强的几个参数几乎恢复正常。最后，我们证明血小板可能是HIV-1感染患者中趋化因子调节激活正常T细胞表达和分泌的趋化因子（RANTES）的重要来源。虽然无症状患者未受刺激和受SFLLRN刺激的血小板RANTES释放均增加，但艾滋病患者的血小板特征是该趋化因子的自发释放明显增加，但受SFLLRN刺激的释放减少。综上所述，这些结果首次证明血小板计数正常的HIV-1感染患者血小板活化增加，这可能代表了HIV-1感染中一种先前未被认识的免疫致病因素。
