Regulation of alpha 1-antitrypsin synthesis by granulocyte macrophage colony-stimulating factor in the U937 promonocytic cell line.
Undifferentiated U937 cells possess low numbers (approximately 1,100 per cell) of receptors for granulocyte macrophage colony-stimulating factor (GMCSF). The receptors present are of at least two types with different affinities. A small number (less than 200 per cell) are of higher affinity (approximate Kd 97pM), and a larger number (approximately 900 per cell) are of lower affinity (approximate Kd 680pM). Following differentiation with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (PMA), the differentiated cells express a reduced number of receptors (approximately 680 per cell). These receptors are present as a single class with an approximate affinity of 230pM (Kd). The undifferentiated cells were responsive to GMCSF and this cytokine caused a seven-fold increase in accumulation of alpha 1-antitrypsin (alpha 1AT) compared to the control cells. This was accompanied by a similar increase in alpha 1ATmRNA, which suggests that the rate of alpha 1AT accumulation was regulated at the transcriptional level. After differentiation with PMA, alpha 1AT accumulation was not influenced by GMCSF, although the cells continued to bind the cytokine. These results imply that U937 cells do respond to GMCSF and this event involves binding of the ligand to a small number of specific cell surface receptors only present in the undifferentiated cells. Furthermore the response of these cells (in terms of alpha 1AT production) is associated with the type of GMCSF receptors expressed.
Afford
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SC
General Hospital, Birmingham, U.K.
Burnett
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D
Stockley
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RA
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D000515:alpha 1-Antitrypsin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate