OPIOID EFFECTS ON BONE MARROW AND T-CELLS

获得性免疫缺陷综合症（艾滋病）现在被认为是 这是本世纪对人类健康最严重的威胁。 由于一个大的， 越来越多的艾滋病受害者是海洛因滥用者， 通过共用注射器感染艾滋病毒， 海洛因和相关的阿片类药物对这种发展的可能影响 疾病是一个主要问题。 大量研究表明， 阿片类药物对这种疾病的发展是一个主要问题。 大 许多研究表明，阿片类药物改变了广泛的免疫功能。 在体内和体外的功能，包括T细胞增殖，自然 杀伤细胞活性、单核细胞趋化性和对植入 肿瘤的 然而，很少有研究检查阿片类药物的可能影响 这些过程产生免疫活性细胞，因此可能 最直接影响艾滋病的发展。 这些过程包括（1） 多能干细胞分化形成淋巴样细胞 来自骨髓的细胞;和（2）白细胞介素-2（IL-2）的产生 T细胞对抗原或有丝分裂原的反应，导致不确定的 这些细胞的增殖。 我们建议详细研究 内源性和外源性阿片类药物在这些过程中的作用。 我们将彻底描述阿片类药物对（1）分化的影响， 将来自小鼠的多能干细胞群转化为淋巴样、骨髓样和 红系细胞集落在体内和体外，和生长因子的能力 M-CSF、促红细胞生成素（EPO）和IL-3逆转这些作用;和（2） 成熟的鼠T细胞产生IL-2和应答 外源性IL-2。 我们还将确定和定量内源性阿片类药物， 干细胞和成熟T细胞，并确定 分化和增殖，分别在这些和 这些细胞中的阿片受体。 最后，我们将开始尝试 纯化T细胞上的阿片受体，并探索其在 介导阿片样物质对T细胞增殖的作用。 这些研究应 提高我们对药物滥用如何增加艾滋病毒风险的认识- 感染者发展为艾滋病。 也可能导致临床 可以增强免疫效应细胞再生的操作 被艾滋病摧毁的组织

Acquired immune deficiency syndrome (AIDS) is now recognized to be one of the most serious threats to human health in this century. Since a large, and growing, proportion of AIDS victims are heroin abusers who have become infected with the AIDS virus (HIV) through sharing of syringes, the possible effects of heroin and related opioids on the development of this disease is a major concern. A large number of studies indicate that opioids on the development of this disease is a major concern. A large number of studies indicate that opioids alter a wide range of immune functions in vivo and in vitro, including T-cell proliferation, natural killer cell activity, monocyte chemotaxis, and response to implanted tumors. However, few studies have examined the possible effects of opioids on those processes that generate immuno-competent cells, and which thus may most directly affect the development of AIDS. These processes include (1) the formation of lymphoid cells by differentiation of pluripotent stem cells from the bone marrow; and (2) the production of interleukin-2 (IL-2) by T-cells in response to an antigen or mitogen, which leads to indefinite proliferation of these cells. We propose to make a detailed examination of the role of endogenous and exogenous opioids in these processes. We will thoroughly characterize opioid effects on (1) differentiation of pluripotent stem cell population from mice into lymphoid, myeloid, and erythroid colonies in vivo and in vitro, and the ability of growth factors M-CSF, erythropoietin (EPO), and IL-3 to reverse these effects; and (2) the ability of mature murine T-cells to produce IL-2 and to respond to exogenous IL-2. We will also identify and quantitate endogenous opioids in both stem cells and mature T-cells, and determine the effects of differentiation and proliferation, respectively, on the levels of these and of opioid receptors in these cells. Finally, we will begin attempts to purify opioid receptors present on T-cells, and explore their role in mediating opioid effects on T-cell proliferation. These studies should increase our understanding of how drug abuse increases the risk of HIV- infected individuals for developing AIDS. They may also lead to clinical manipulations that could enhance the regeneration of immune effector cells that are destroyed by AIDS.