The effect of IFN-gamma and colony-stimulating factors on the expression of neutrophil cell membrane receptors.

Abstract

The recombinant cytokines IFN-gamma, granulocyte-macrophage (GM)-CSF, and granulocyte (G)-CSF are all known to affect the function of neutrophils. We have investigated their ability to alter the surface expression of neutrophil Fc gamma R and CR. FcRI, formerly considered to be mononuclear phagocyte specific, was found on a variable percentage of neutrophils after 12 h of tissue culture. These levels could be readily enhanced by IFN-gamma at 0.5 U/ml suggesting that neutrophil FcRI is extremely sensitive IFN-gamma. In addition, membrane expression of FcRIII, the most abundant receptor of neutrophils, could also be increased by IFN-gamma and by GM-CSF and G-CSF. However, the opposite effect was observed in samples in which the initial levels of FcRIII were high. In these situations IFN-gamma and GM-CSF caused a decrease in receptor expression. No consistent alterations were found in the levels of FcRII. Cytokine-induced increases in both FcRI and FcRIII were not evident within the first hour of treatment suggesting that these molecules are not available in an intracellular compartment but must be newly synthesized. In contrast, the CR, CR1 and CR3, could be rapidly induced by GM-CSF indicating that this cytokine causes the mobilization of preformed molecules to the membrane. G-CSF and IFN-gamma did not alter the expression of CR1 and CR3. Thus, the very different effects of IFN-gamma, GM-CSF, and G-CSF suggest that the neutrophil functional profile will be distinctively affected by exposure to each of these cytokines.