[In vitro differentiation of leukaemic promyelocytes (HL-60): effect on beta-adrenergic receptors and adenylate cyclase activity].
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.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D009000:Monocytes / Q000166:cytology; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D014212:Tretinoin; C032975:12-O-tetradeca-2,4,6,8-tetranoylphorbol-13-acetate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate
In-vitro-Differenzierung leukämischer Promyelozyten (HL-60): Verhalten der beta-adrenergen Rezeptoren und der Adenylatzyklaseaktivität.