Induction of telomerase activity during development of human mast cells from peripheral blood CD34+ cells: comparisons with tumor mast-cell lines.
To further characterize the development of mast cells from human hemopoietic pluripotent cells we have investigated the expression of telomerase activity in cultured human peripheral blood CD34+ cells, and CD34+ /CD117+ /CD13+ progenitor mast cells selected therefrom, with the idea that induction of telomerase is associated with clonal expansion of CD34+ /CD117+ /CD13+ cells. A rapid increase in telomerase activity preceded proliferation of both populations of cells in the presence of stem cell factor and either IL-3 or IL-6. The induction was transient, and telomerase activity declined to basal levels well before the appearance of mature mast cells. Studies with pharmacologic inhibitors suggested that this induction was initially dependent on the p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase, but once cell replication was underway telomerase activity, but not cell replication, became resistant to the effects of inhibitors. Tumor mast cell lines, in contrast, expressed persistently high telomerase activity throughout the cell cycle, and this expression was unaffected by inhibitors of all known signaling pathways in mast cells even when cell proliferation was blocked for extended periods. These results suggest that the transient induction of telomerase activity in human progenitor mast cells was initially dependent on growth factor-mediated signals, whereas maintenance of high activity in tumor mast cell lines was not dependent on intracellular signals or cell replication.
Chaves-Dias
C
C
Laboratory of Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hundley
T R
TR
Gilfillan
A M
AM
Kirshenbaum
A S
AS
Cunha-Melo
J R
JR
Metcalfe
D D
DD
Beaven
M A
MA
D000081:Acetamides / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis*; D018826:CD13 Antigens / Q000096:biosynthesis; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015471:Leukemia, Basophilic, Acute / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D019089:Stem Cell Factor / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000081:Acetamides; D000730:Androstadienes; D018952:Antigens, CD34; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D006133:Growth Substances; D007093:Imidazoles; D007377:Interleukin-3; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D011725:Pyridines; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D019098:Telomerase; D018826:CD13 Antigens; C014026:hexamethylene bisacetamide; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D000077191:Wortmannin