Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor-mediated agonists.
The effects of hematopoietic growth factors on human monocyte superoxide (O2-) release were investigated by using purified human monocytes in suspension. Among growth factors studied, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), and interleukin-3 (IL-3) primed human monocytes and enhanced O2- release stimulated by the receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate, which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of cells with 1 to 5 ng/mL (0.07 to 0.34 nmol/L) GM-CSF, 50 to 100 ng/mL (0.5 to 1.1 nmol/L) M-CSF, or 10 to 20 ng/mL (0.6 to 1.3 nmol/L) IL-3 for 10 minutes at 37 degrees C. Potency of the maximal priming effects on FMLP- or Con A-induced O2- release was GM-CSF greater than M-CSF = IL-3. The combination of the optimal concentrations of any two CSFs resulted in the effect of more potent priming agent alone. Enhancement of O2- release by GM-CSF was observed over the complete range of effective concentrations of FMLP (10(-8) to 10(-6) mol/L). The pretreatment of monocytes with granulocyte-CSF (50 ng/mL), interferon-gamma (1,000 U/mL), or IL-4 (20 ng/mL) for 10 minutes at 37 degrees C had no effect on O2- release stimulated by FMLP or Con A. These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation.
Yuo
A
A
Clinical Research Institute, National Medical Center, Tokyo, Japan.
Kitagawa
S
S
Motoyoshi
K
K
Azuma
E
E
Saito
M
M
Takaku
F
F
D000328:Adult; D002478:Cells, Cultured; D003208:Concanavalin A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010766:Phosphorylation; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007377:Interleukin-3; D003208:Concanavalin A; D013481:Superoxides; D015847:Interleukin-4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate