Modulation by retinoids and interferons of alkaline phosphatase activity in granulocytes induced by granulocyte colony-stimulating factor.
We have previously shown that a factor termed NAP-IF has the capacity to induce neutrophil alkaline phosphatase (NAP) in postmitotic granulocytes (PMGs). Recently, this factor found in cystic fluid of a human squamous cell carcinoma was shown to be identical to granulocyte colony-stimulating factor (G-CSF). In this study we examined whether NAP activity inducible with G-CSF could be modulated by other factors that are present in vivo or those that are known to induce differentiation of hemopoietic cells. Purified natural and recombinant G-CSF (nG-CSF and rG-CSF) induced NAP in PMGs from both normal individuals and patients with chronic myelogenous leukemia. Interferons (IFNs) suppressed expression of NAP by G-CSF. IFN-gamma was a potent inhibitor of G-CSF stimulation: IFN-gamma at 100 U/ml inhibited by greater than 90% the induction of NAP by G-CSF. In contrast, retinol (10(-6) M, a nearly physiological concentration) or all-trans-retinoic acid (10(-6) M) significantly enhanced NAP activity in vitro. Furthermore, the simultaneous addition of 10(-6) M retinol partially reversed the inhibitory action of IFN-gamma on the NAP induction by G-CSF. Our results suggest that NAP activity, which is often abnormal in a variety of diseases, may reflect G-CSF levels in vivo perhaps in concert with a number of other factors including IFNs and retinoids.
Sato
N
N
Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Takatani
O
O
Koeffler
H P
HP
Sato
H
H
Asano
S
S
Takaku
F
F
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D012176:Retinoids / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D012176:Retinoids; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D007372:Interferons; D000469:Alkaline Phosphatase