Balog T, Marotti T, Abramić M, Svoboda-Beusen I, Hrsak I
Department of Molecular Medicine, Institute Ruder Bosković, Zagreb, Croatia.
Immunopharmacology. 1999 Jan;41(1):11-20. doi: 10.1016/s0162-3109(98)00050-2.
We have previously shown that methionine-enkephalin (MENK) alters in dose-dependent fashion the capacity of human neutrophils to produce superoxide anion. The response of neutrophils from different donors was diverse and this effect could be due to variable activity of proteolytic enzymes involved in the degradation of the neuropeptide. In this study, we have demonstrated a highly individual aminopeptidase N (APN) activity of neutrophils from different donors. Preincubation of neutrophils with MENK, but not with the synthetic agonist of the mu (DAGO) or the delta (DPDPE) opioid receptor, down-regulated the APN activity. This was paralleled by a loss in cell surface expression of APN at physiological (10(-10) M) concentrations of MENK. The level of APN activity from different donors correlated with the effect of MENK on superoxide anion release. Neutrophils with low APN activity, if preincubated with MENK, released reduced amounts of superoxide anion. In contrast, neutrophils with high APN activity released increased amounts of superoxide anion after preincubation with MENK. Thus, the highly individual APN activity on the surface of neutrophils from different donors seems to be altered by MENK and to be related to the respiratory burst.
我们之前已经表明,甲硫氨酸脑啡肽(MENK)以剂量依赖性方式改变人类中性粒细胞产生超氧阴离子的能力。来自不同供体的中性粒细胞的反应各不相同,这种效应可能归因于参与神经肽降解的蛋白水解酶的活性变化。在本研究中,我们证明了来自不同供体的中性粒细胞具有高度个体性的氨肽酶N(APN)活性。用MENK而非μ(DAGO)或δ(DPDPE)阿片受体的合成激动剂对中性粒细胞进行预孵育,会下调APN活性。在生理浓度(10^(-10) M)的MENK作用下,APN的细胞表面表达丧失与之平行。来自不同供体的APN活性水平与MENK对超氧阴离子释放的影响相关。APN活性低的中性粒细胞,如果用MENK预孵育,释放的超氧阴离子量减少。相反,APN活性高的中性粒细胞在与MENK预孵育后释放的超氧阴离子量增加。因此,来自不同供体的中性粒细胞表面高度个体性的APN活性似乎会被MENK改变,并与呼吸爆发有关。