Characterization and modulation of cell surface proteases on human myeloblastic (HL-60) cells and comparison to normal myeloid cells.
Human myeloblastic HL-60 cells were probed for cell surface protease activity. A class of bestatin sensitive N-exoaminopeptidases and a dipeptidyl aminopeptidase IV-like enzyme specifically inhibited by DFP and diprotin A were detected at the surface of intact cells, as well as in highly purified HL-60 cell membranes. Cell surface proteolytic activities were investigated in HL-60 cells induced to differentiate into granulocytes or macrophages as well as on normal human myeloid cells. It was found that membrane expression of serine and N-aminopeptidases significantly increased following maturation of the HL-60 cell line and normal monocytes toward the macrophage pathway. In contrast, N-aminopeptidase expression was mainly down-regulated on HL-60 cells differentiated into granulocytes and low activity was paralleled with that expressed by normal blood granulocytes. HL-60 maturation into the granulocyte lineage however did not cause any modulation in membrane DPP IV-like enzyme. Thus, selective expression of cell surface proteases along the myeloid lineage provides a useful model system for determining the possible influence of such enzymes on normal and malignant myeloid cells.
Unité 196 INSERM, Institut Curie, Paris, France.
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Laouar
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Bauvois
D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000201:enzymology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4