Paietta E
Wien Klin Wochenschr. 1983 May 13;95(10):336-44.
In the present study, the expression of beta-adrenergic receptors, the activity of the enzyme adenylate cyclase (AC), and the intracellular concentration of cyclic adenosine 3',5'-monophosphate (cAMP) were investigated in HL-60 cells before and after their differentiation to monocytic or more mature granulocytic cells. Treatment of the HL-60 promyelocytes with 12-O-tetradecanoylphorbol 13-acetate or human interleukin 2 resulted in the appearance of cells with monocytic characteristics (morphology, non-specific esterase, adherence, reaction with a monocyte-specific monoclonal antibody). Induction with retinoic acid resulted in differentiation to cells with typical features of mature granulocytes (morphology, peroxidase, nitro-blue tetrazolium reduction). During maturation to monocytes, the density of beta-adrenergic receptors decreased, whereas it remained constant during maturation to granulocytes. In comparison with normal circulating monocytes or polymorphonuclear granulocytes, expression of beta-adrenergic receptors on the surface of the differentiated HL-60 cells was low. Activation of AC by the hormones isoproterenol, prostaglandin E1, and histamine generally decreased with HL-60 maturation and enzyme activities were markedly below those measured in normal peripheral leukocytes. In the induced monocytic HL-60 cells, the weak effectiveness of isoproterenol was due to the loss of beta-adrenergic receptors. In the induced granulocytic HL-60 cells, the reduced hormonal AC activation could be explained by the impaired coupling between hormone receptors and catalytic enzyme unit. The concentration of intracellular cAMP after differentiation of HL-60 cells reflected the increase in basal AC activity and the decrease in hormone stimulation of the enzyme. Our data indicate that HL-60 cells induced to differentiate possess some monocyte- and granulocyte-like properties, but do not meet several important functional criteria of their new cell identities.
在本研究中，对HL-60细胞向单核细胞或更成熟粒细胞分化前后的β-肾上腺素能受体表达、腺苷酸环化酶（AC）活性以及细胞内3',5'-环磷酸腺苷（cAMP）浓度进行了研究。用12-O-十四烷酰佛波醇-13-乙酸酯或人白细胞介素2处理HL-60早幼粒细胞，导致出现具有单核细胞特征的细胞（形态、非特异性酯酶、黏附性、与单核细胞特异性单克隆抗体的反应）。用维甲酸诱导导致分化为具有成熟粒细胞典型特征的细胞（形态、过氧化物酶、硝基蓝四氮唑还原）。在向单核细胞成熟的过程中，β-肾上腺素能受体密度降低，而在向粒细胞成熟的过程中其保持恒定。与正常循环单核细胞或多形核粒细胞相比，分化后的HL-60细胞表面β-肾上腺素能受体的表达较低。异丙肾上腺素、前列腺素E1和组胺等激素对AC的激活通常随HL-60细胞成熟而降低，酶活性明显低于正常外周白细胞中的测定值。在诱导的单核细胞样HL-60细胞中，异丙肾上腺素的低效性是由于β-肾上腺素能受体的丧失。在诱导的粒细胞样HL-60细胞中，激素对AC激活的降低可解释为激素受体与催化酶单位之间的偶联受损。HL-60细胞分化后细胞内cAMP的浓度反映了基础AC活性的增加和激素对该酶刺激的减少。我们的数据表明，诱导分化的HL-60细胞具有一些单核细胞样和粒细胞样特性，但不符合其新细胞身份的几个重要功能标准。
