Stefano G B, Salzet M, Rialas C M, Mattocks D, Fimiani C, Bilfinger T V
Multidisciplinary Center for the Study of Aging, Neuroscience Research Institute, State University of New York/College at Old Westbury, 11568, USA.
Int J Cardiol. 1998 Apr 30;64 Suppl 1:S3-13. doi: 10.1016/s0167-5273(98)00030-8.
We demonstrate that immediate exposure to gp120 (5 min; 0.1 microg/ml) results in a significant shift of the macrophage population to an amoeboid and motile category (P<0.01; 91.7+/-5.5 vs. a control value of 42.4+/-4.2) and prior exposure with anti-gp120 antagonizes this shift. Acute exposure of the macrophages to morphine (10(-6) M) or anandamide (10(-6) M) resulted in the cells rounding up (shape factors of 0.84 and 0.87 respectively) and becoming non-motile. The action is blocked by prior treatment with the specific antagonists naloxone and SR 141716A. Chronic exposure (6 h) of the cells to all three agents resulted in a random migration pattern. Further, all agents blocked chemotaxis induced by DAMA and IL-1. Observation of the cells behavior during chronic exposure revealed a sporadic activity pattern with gp120 whereas morphine and anandamide first induced a period of inactivity which is followed by a period of activity (chemokinesis). Recent work from our laboratory has demonstrated that both morphine and anandamide acutely stimulate constitutive macrophage nitric oxide (NO) release, which then induces macrophage rounding and inactivity. It was therefore of interest to examine their behavior by exposing macrophages to the NO-donor SNAP. In a concentration dependent manner SNAP exhibited the same behavioral actions as both substances of abuse. Given this, we next determined if macrophages exposed to gp120 would release NO. We demonstrated that NO was released only when exposed to morphine and anandamide not gp120. Thus. the chemokinetic inducing activities of these agents may be the basis for excitotoxin liberation in neural tissues and/or a higher viral load in various organ systems since cellular adherence and random migration are stimulated.
我们证明，立即暴露于gp120（5分钟；0.1微克/毫升）会导致巨噬细胞群体显著转变为阿米巴样和运动性类别（P<0.01；91.7±5.5，而对照值为42.4±4.2），且预先用抗gp120处理可拮抗这种转变。巨噬细胞急性暴露于吗啡（10⁻⁶ M）或花生四烯乙醇胺（10⁻⁶ M）会导致细胞变圆（形状因子分别为0.84和0.87）并失去运动性。该作用可被预先用特异性拮抗剂纳洛酮和SR 141716A处理所阻断。细胞长期暴露（6小时）于这三种药物会导致随机迁移模式。此外，所有药物均阻断了由DAMA和IL-1诱导的趋化作用。在长期暴露期间观察细胞行为发现，gp120呈现出散发性活动模式，而吗啡和花生四烯乙醇胺首先诱导一段无活动期，随后是一段活动期（化学动力学）。我们实验室最近的研究表明，吗啡和花生四烯乙醇胺均可急性刺激巨噬细胞组成型释放一氧化氮（NO），进而诱导巨噬细胞变圆和无活动。因此，通过将巨噬细胞暴露于NO供体SNAP来检查它们的行为很有意义。SNAP以浓度依赖方式表现出与两种滥用物质相同的行为作用。鉴于此，我们接下来确定暴露于gp120的巨噬细胞是否会释放NO。我们证明，只有在暴露于吗啡和花生四烯乙醇胺时而不是gp120时才会释放NO。因此，这些药物的化学动力学诱导活性可能是神经组织中兴奋性毒素释放和/或各种器官系统中更高病毒载量的基础，因为细胞黏附和随机迁移受到刺激。
