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.
Rossman
M D
MD
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Ruiz
P
P
Comber
P
P
Gomez
F
F
Rottem
M
M
Schreiber
A D
AD
D000818:Animals; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000276:immunology*; D012333:RNA, Messenger / Q000097:blood; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012397:Rosette Formation; D012756:Sheep / Q000097:blood
D007074:Immunoglobulin G; D012333:RNA, Messenger; D011961:Receptors, Fc; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor