Secretion of granulocyte-macrophage colony-stimulating factor by human blood monocytes is stimulated by engagement of Fc gamma receptors type I by solid-phase immunoglobulins requiring high-affinity Fc-Fc gamma receptor type I interactions.
Despite reports on the secretion of granulocyte-macrophage-colony-stimulating factor (GM-CSF) by murine peritoneal macrophages in response to inflammatory stimuli, the ability of human monocytes to generate this growth factor has remained doubtful. Neither endotoxin, phorbol compounds, nor inflammatory cytokines have been shown to elicit GM-CSF by these cells. Our present studies indicate that exposure of monocytes to solid-phase murine IgG2a, but not to murine IgG1 and thus cross-linkage of the 72-kDa Fc gamma RI results in transcription of the GM-CSF gene, accumulation of stable GM-CSF mRNA and finally in release of biologically active GM-CSF protein. Cross-linking of Fc gamma RI by a murine anti-Fc gamma RI monoclonal antibody and goat anti-mouse antibody failed, however, to stimulate GM-CSF release. This suggests that high affinity Fc-Fc gamma RI interactions are required for induction of expression of GM-CSF by monocytes.
Herrmann
F
F
Department of Hematology and Oncology, University of Freiburg, FRG.
De Vos
S
S
Brach
M
M
Riedel
D
D
Lindemann
A
A
Mertelsmann
R
R
D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000502:physiology*; D007074:Immunoglobulin G / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG
D000943:Antigens, Differentiation; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D016178:Granulocyte-Macrophage Colony-Stimulating Factor