MORPHINE PROMOTES THE GROWTH OF HIV-1 IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR CELL COCULTURES
MORPHINE PROMOTES THE GROWTH OF HIV-1 IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR CELL COCULTURES
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DOI：
10.1097/00002030-199009000-00006
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发表时间：
1990-09-01
期刊：
影响因子：
3.8
通讯作者：
BALFOUR, HH
中科院分区：
文献类型：
--
作者：
PETERSON, PK;SHARP, BM;BALFOUR, HH
由于吗啡已被证明可以改变人类T淋巴细胞和单核细胞的功能，我们假设吗啡会促进这些细胞中HIV-1的生长。为了验证这一假设，采用共培养试验，其中包括来自正常供体的植物血凝素（PHA）激活的外周血单个核细胞（PBMC）和感染了来自无症状患者HIV-1AT的病毒分离物的PBMC。通过共培养上清液中p24抗原的浓度反映，含有吗啡的共培养显著增加了HIV-1AT的生长。在吗啡浓度为10-12 m时，观察到钟形剂量-反应曲线，生长增加了3至4倍。吗啡增强HIV-1AT生长需要与pha激活的供体PBMC相互作用。此外，吗啡对HIV-1AT生长的增强具有立体特异性，可被纳洛酮和β所拮抗。-funaltrexamine表明阿片受体机制的参与。这些发现为阿片类药物如何在静脉注射吸毒者的HIV-1发病机制中作为辅助因素提供了额外的解释。
Because morphine has been shown to alter the function of human T lymphocytes and monocytes, we postulated that morphine would promote the growth of HIV-1 in these cells. To test this hypothesis, a coculture assay was used consisting of phytohemagglutinin in (PHA)-activated peripheral blood mononuclear cells (PBMC) from normal donors and PBMC which had been infected with a viral isolate from an asymptomatic patient, HIV-1AT. The growth of HIV-1AT, as reflected by the concentration of p24 antigen in coculture supernatants, was markedly increased in cocultures that contained morphine. A bell-shaped dose-response curve was observed with three- to fourfold increased growth at a morphine concentration of 10-12 M. Augmentation of HIV-1AT growth by morphine required an interaction with the PHA-activated donor PBMC. Furthermore, potentiation of HIV-1AT growth by morphine was stereospecific and was antagonised by naloxone and .beta.-funaltrexamine indicating involvement of an opiate receptor mechanism. These findings provide an additional explanation of how opiates could act as a cofactor in the pathogenesis of HIV-1 in intravenous drug users.