MODULATION OF SIMIAN AIDS BY OPIOIDS

阿片类药物对猿猴艾滋病的调节

• 批准号: 6277909
• 负责人: RONALD Y CHUANG
• 金额: $ 8.13万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277909
• 关键词: AIDS; Mammalia; Primates; animal tissue; immunology; infection; inflammation; lymphatic system; substance abuse related disorder; virus

Significance Chemokines, characterized as pro-inflammatory chemicals made by the immunesystem, consist of a family of low molecular weight proteins with potent in vitro chemotactic activity causing leukocyte accumulation in vivo. In general, the a chemokines (C-X-C, C denotes cysteines) such as interleukin-8 (IL-8) induce chemotaxis in polymorphonuclear cells (PMN) and have no effect on monocytes, while the b chemokines (C-C) such as RANTES, MIP-1a and MIP-1b predominantly chemoattract monocytes, macrophages and T cells. Objectives This study determined the effect of opioid treatment on the chemotactic functions of PMN and monocytes isolated from monkey leukocytes using a 48-well chemotaxis chamber. Monkey PMN or monocytes were treated with morphine or morphine antagonist for 1 hr at 370C, and the number of cells migrating toward 200 ng/ml IL-8 (for PMN) or 100 ng/ml RANTES (for monocytes) were scored. Results Inhibition of chemotaxis was seen with all animal samples after treatment with morphine at 10-4 M. Decreasing concentrations of morphine showed increasing chemotaxis with 10-14 M concentration bringing the number of cells equal to that of positive control (no morphine treatment.) Naloxone, an antagonist to morphine, was added 30 minutes prior to the addition of morphine sulfate to the cells. When the morphine concentration used was 10-6 M, naloxone at 10-4 M was able to reverse the morphine inhibitory effect on PMN chemotaxis by 85% while naloxone at equal molar of morphine (10-6 M) reversed the inhibition by 69%. Similar morphine and morphine/naloxone effects on monocyte chemotaxis toward RANTES were observed. These studies suggest that opiate abuse caused defects in host defense and may have implications for the enhanced immunosuppression seen with AIDS patients of opiate users. Future Directions Future directions will include the evaluation of the effects of other opioids and opioid antagonists in this study. KEYWORDS rhesus monkeys, peripheral blood mononuclear cells, monocytes, PMN, chemokines, chemotaxis, morphine and other opioids

意义趋化因子，以促炎为特征 由免疫系统产生的化学物质，包括一个低 具有有效体外趋化活性的分子量蛋白质 导致白细胞在体内积聚。 一般来说，a趋化因子 （C-X-C，C表示半胱氨酸）如白细胞介素-8（IL-8）诱导 多形核白细胞（PMN）的趋化性， 单核细胞，而B类趋化因子（C-C）如RANTES、MIP-1 a和 MIP-1b主要趋化单核细胞、巨噬细胞和T细胞。 目的本研究旨在确定阿片类药物治疗对 猴中性粒细胞和单核细胞的趋化功能 使用48孔趋化室测定白细胞。 猴PMN或 单核细胞用吗啡或吗啡拮抗剂处理1小时 在37 ℃下，向200 ng/ml IL-8迁移的细胞数（对于 PMN）或100 ng/ml RANTES（对于单核细胞）进行评分。 结果 在给药后，所有动物样品均观察到趋化性抑制。 用10-4 M吗啡处理。递减浓度的 吗啡在10-14 M浓度下表现出趋化性增加 使细胞数目等于阳性对照（无 吗啡治疗）。吗啡拮抗剂纳洛酮加入30 在向细胞中加入硫酸吗啡之前10分钟。 当 吗啡浓度为10-6 M，纳洛酮浓度为10-4 M， 能够逆转吗啡对PMN趋化性的抑制作用， 85%，而等摩尔吗啡（10-6 M）的纳洛酮逆转了 抑制率为69%。 吗啡和吗啡/纳洛酮对 观察到单核细胞对RANTES的趋化性。 这些研究 表明阿片类药物滥用导致宿主防御缺陷， 艾滋病患者免疫抑制增强的意义 阿片类药物使用者。 未来方向未来方向 包括评价其他类阿片和类阿片 在这项研究中， 关键词恒河猴，外周血 单核细胞，单核细胞，中性粒细胞，趋化因子，趋化性，吗啡 和其他类阿片