Lang M E, Jourd'Heuil D, Meddings J B, Swain M G
Department of Internal Medicine, University of Calgary, Alberta, Canada.
Gastroenterology. 1995 May;108(5):1479-86. doi: 10.1016/0016-5085(95)90697-5.
BACKGROUND/AIMS: Endogenous opioids accumulate in plasma in cholestasis. Furthermore, immune cells have opioid receptors, and endogenous opioids have immunomodulatory effects. This study examined the expression of opioid receptors on peripheral white blood cells in rats with acute cholestasis after bile duct resection (BDR).
Five days after surgery, white blood cells were isolated from peripheral blood. To determine total opioid binding, cells from either BDR or sham-resected rats were incubated with a fluorescently labeled opioid receptor antagonist. Specific opioid binding was determined by preincubating the cells with a 100-fold molar excess of unlabeled naltrexone or with one of two opioid receptor agonists: (D-Ala2, D-Leu5)-enkephalin (delta receptor) or (D-Ala2, MePhe4, Gly-ol5)enkephalin (mu receptor). The proportion of neutrophils, lymphocytes, and monocytes with specific delta or mu opioid receptors was determined by flow cytometric analysis.
Opioid receptors on neutrophils were unaffected by BDR, whereas the lymphocyte population of BDR rats had an increased binding to delta receptors (2.6% +/- 1.1% for sham vs. 7.3% +/- 1.4% for BDR; P < 0.02) and monocytes from BDR rats had an increased binding to mu receptors (7.7% +/- 0.9% for sham vs. 17.9% +/- 2.3% for BDR; P < 0.0001).
The selective increase of delta-receptor binding on lymphocytes and mu-receptor binding on monocytes suggests that, in acute cholestasis, opioid-mediated effects on white blood cell function may be altered.
背景/目的：内源性阿片类物质在胆汁淤积时会在血浆中蓄积。此外，免疫细胞具有阿片受体，内源性阿片类物质具有免疫调节作用。本研究检测了胆管切除（BDR）后急性胆汁淤积大鼠外周血白细胞上阿片受体的表达。
术后5天，从外周血中分离白细胞。为了测定总的阿片结合，将BDR大鼠或假手术切除大鼠的细胞与荧光标记的阿片受体拮抗剂孵育。通过用100倍摩尔过量的未标记纳曲酮或两种阿片受体激动剂之一预孵育细胞来测定特异性阿片结合：（D-丙氨酸2，D-亮氨酸5）脑啡肽（δ受体）或（D-丙氨酸2，甲基苯丙氨酸4，甘氨醇5）脑啡肽（μ受体）。通过流式细胞术分析确定具有特异性δ或μ阿片受体的中性粒细胞、淋巴细胞和单核细胞的比例。
中性粒细胞上的阿片受体不受BDR影响，而BDR大鼠的淋巴细胞群体与δ受体的结合增加（假手术组为2.6%±1.1%，BDR组为7.3%±1.4%；P<0.02），BDR大鼠的单核细胞与μ受体的结合增加（假手术组为7.7%±0.9%，BDR组为17.9%±2.3%；P<0.0001）。
淋巴细胞上δ受体结合和单核细胞上μ受体结合的选择性增加表明，在急性胆汁淤积时，阿片介导的对白细胞功能的影响可能会改变。
