MODULATION OF MACROPHAGE FC-GAMMA RECEPTORS BY RGM-CSF

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor being used increasingly to support white blood cell counts in hematologic disorders. Since the survival of IgG-sensitized cells following blood transfusions and the clearance of immune complexes are important in these disorders, we investigated the effect of GM-CSF on the Fc(gamma) receptors largely responsible for this immune clearance. Human monocytes were cultured in buffer or 100 U/mL of recombinant GM-CSF (rGM-CSF) for 48 hours. Flow cytometry was used to evaluate changes in the expression of the three Fc(gamma) receptors. Fc(gamma)RII was the only Fc(gamma) receptor significantly increased by rGM-CSF. This increase in Fc(gamma)RII surface protein was correlated with an increase in macrophage binding of erythrocytes sensitized with IgG. In addition, an increase in monocyte binding of IgG-sensitized RBCs was observed in RBCs sensitized with murine IgG2b antibody, which preferentially binds to Fc(gamma)RII. rGM-CSF also increased the monocyte Fc(gamma)RII-dependent low-affinity binding site for trimeric IgG. Furthermore, rGM-CSF was observed to increase the expression of monocyte Fc(gamma)RII mRNA, including that for Fc(gamma)RIIA. Thus, these studies demonstrate that GM-CSF increases monocyte Fc(gamma)RII expression and function and suggests that a similar process may be present in vivo. This effect may be either beneficial (increased clearance of immune complexes) and/or detrimental (increased transfusion requirements) in select patients.