Neopterin release by myeloid leukaemic cells can be synergistically augmented by 1,25-dihydroxyvitamin D3 in combination with gamma interferon or granulocyte-macrophage colony stimulating factor.
Neopterin is a pteridine molecule released by immune activated monocytes. Monocytic maturation may be induced in acute myeloid leukaemia (AML) blasts and the U937 leukaemic cell line by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], an effect which is augmented by both gamma interferon (IFN) or granulocyte-macrophage colony stimulating factor (GM-CSF). We have demonstrated that, while 1,25(OH)2D3 and GM-CSF alone have little effect, both IFN and GM-CSF act synergistically with 1,25(OH)2D3 to increase neopterin secretion in the U937 cell line. Neopterin secretion was associated with, but not necessarily dependent on, the degree of phenotypic differentiation achieved by cells. Neopterin secretion was also synergistically enhanced in AML blasts by the action of 1,25(OH)2D3 in combination with IFN but not GM-CSF; secretion was enhanced in AML blasts without concomitant evidence of phenotypic maturation. We have shown that the monocytoid cell line U937, under appropriate conditions, may secrete neopterin in response to stimulatory agents other than IFN. In addition, the distinct difference in the pattern of response to the combination of 1,25(OH)2D3 with GM-CSF compared with that of 1,25(OH)2D3 plus IFN suggests that the augmentation of 1,25(OH)2D3 effect by IFN and GM-CSF is mediated by separate mechanisms.
Kelsey
S M
SM
Department of Haematology, Royal London Hospital, Whitechapel, England.
Coldwell
R D
RD
Makin
H L
HL
Syndercombe-Court
D
D
Newland
A C
AC
D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute; D019798:Neopterin; D014407:Tumor Cells, Cultured
D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002117:Calcitriol