The recombinant (r) cytokines interferon-γ (rIFN-γ), granulocyte/macrophage-colony stimulating factor (rGM-CSF) and tumor necrosis factor-α (rTNF-α) all activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil Fc-receptor (FcR)-mediated phagocytosis and membrane expression of FcR, particularly FcRII and FcRIII. A short treatment (≥ 15 min) of neutrophils with rGM-CSF and rTNF-α at concentrations ≥ 62.5 U/ml significantly increased their ability to bind and phagocytize IgG-coated erythrocytes (EA). Both cytokines also showed more enhancing activity when suboptimally sensitized EA were used for binding and ingestion assays. A similar treatment of neutrophils with rIFN-γ at doses up to 500 U/ml was ineffective. The effect of rGM-CSF and rTNF-α was blocked by a monoclonal anti-GM-CSF antibody and by a polyclonal anti-TNF-α antibody respectively, thus establishing that the cytokines were responsible for the activity of the recombinant preparations. The cytokine-induced enhancement of FcR-mediated phagocytosis did not correlate with an enhancement of FcRII membrane expression on treated neutrophils; rGM-CSF significantly increased FcRIII expression, but rTNF-α and rIFN-γ were both ineffective in this respect. Since different roles of FcRII and FcRIII have been reported on ligand binding and ingestion, we also studied the effect of rGM-CSF and rTNF-α on the functional properties of these FcR, using specific monoclonal antibodies (mAbs). In the blocking experiments the pretreatment of neutrophils with rGM-CSF and rTNF-α did not modify the blocking properties of either anti-FcRII or anti-FcRIII mAbs, suggesting that cytokine-pretreatment does not affect the individual contribution of each type of FcR to ligand binding and internalization. Our data point to a new activity for both rGM-CSF and rTNF-α in augmenting FcR-mediated phagocytosis on neutrophils, but the mechanism of this enhancement remains to be elucidated.
|Titolo:||The effect of cytokines on human neutrophil Fc receptor-mediated phagocytosis|
CAPSONI, FRANCO (Primo)
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||1991|
|Appare nelle tipologie:||01 - Articolo su periodico|