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μ-阿片受体激动剂对趋化因子诱导的猴白细胞趋化作用的抑制

Inhibition of chemokine-induced chemotaxis of monkey leukocytes by mu-opioid receptor agonists.

作者信息

Choi Y, Chuang L F, Lam K M, Kung H F, Wang J M, Osburn B I, Chuang R Y

机构信息

Department of Medical Pharmacology & Toxicology, University of California, Davis 752-7710, USA.

出版信息

In Vivo. 1999 Sep-Oct;13(5):389-96.

Abstract

It is recognized that chemotaxis and phagocytosis constitute the first line of defense in the immune system, and chemokines function mainly as chemoattractants for phagocytic cells, recruiting monocytes and neutrophils from the blood to sites of infection. In this study, chemotaxis of monkey leukocytes was evaluated using human chemokines IL-8 (interleukin-8), MIP-1 beta and RANTES as the chemoattractants, and the effects of micro-opioid receptor agonists, morphine, DAMGO, methadone and endomorphine, on the efficiency of chemotaxis were examined. It was found that human chemokines served well as chemoattractants for monkey leukocytes, and similar to the human system, chemokine-induced chemotaxis of monkey leukocytes was inhibited in the presence of micro-opioid receptor agonists. The inhibition could be reversed by naloxone, a specific micro-opioid receptor antagonist. These studies further support the value of the monkey model for drug abuse studies in humans, as well as suggest that opioids such as morphine may alter immune functions through micro-opioid receptors on leukocytes.

摘要

人们认识到趋化作用和吞噬作用构成了免疫系统的第一道防线,趋化因子主要作为吞噬细胞的趋化剂,将血液中的单核细胞和中性粒细胞招募到感染部位。在本研究中,使用人类趋化因子白细胞介素-8(IL-8)、巨噬细胞炎症蛋白-1β(MIP-1β)和调节激活正常T细胞表达和分泌因子(RANTES)作为趋化剂来评估猴白细胞的趋化作用,并研究了微阿片受体激动剂吗啡、DAMGO、美沙酮和内吗啡肽对趋化效率的影响。结果发现,人类趋化因子对猴白细胞起到了良好的趋化剂作用,并且与人类系统相似,在存在微阿片受体激动剂的情况下,趋化因子诱导的猴白细胞趋化作用受到抑制。这种抑制作用可被特异性微阿片受体拮抗剂纳洛酮逆转。这些研究进一步支持了猴模型在人类药物滥用研究中的价值,同时也表明吗啡等阿片类药物可能通过白细胞上的微阿片受体改变免疫功能。

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