Function and regulation of a murine macrophage-specific IgG Fc receptor, Fc gamma R-alpha.
Ligand binding specificities of two cloned murine Fc gamma Rs (Fc gamma R-alpha, Fc gamma R-beta [9]) were determined by gene transfer into Fc gamma R negative cell lines. Both receptors were expressed as full-length molecules capable of IgG immune complex binding that was inhibitable by the mAb 2.4G2. The ligand binding profiles of these receptors were indistinguishable whereby both bound immune-complexed mouse IgG1, IgG2a, and IgG2b, but not IgG3. Neither receptor could bind monomeric IgG2a, indicating these receptors to be low-affinity IgG Fc receptors. Accumulation of the Fc gamma R-alpha mRNA can be induced with murine IFN-gamma at a concentration of 200 U/ml in the macrophage-like cell lines RAW 264.7 and J774a. The time course for induction indicates that the mRNA accumulation is transient but does not return to the uninduced level even after 50 h of treatment. Fc gamma R-beta mRNA was not induced by IFN-gamma, rather its expression was down modulated in mouse peritoneal macrophages. Both RAW and J774a cells lines exhibited increased receptor levels after IFN-gamma stimulation as measured by 125I-2.4G2 and ligand binding. In the absence of IFN-gamma, the RAW and J774a cell lines were minimally phagocytic, while P388D1 cells were actively phagocytic. In the presence of IFN-gamma, however, RAW 264.7 and J774a cells were induced to become actively phagocytic. Induction of Fc gamma R-alpha mRNA and protein by IFN-gamma may be part of the process by which macrophages become activated to engulf antibody-coated particles.
Weinshank
R L
RL
Dewitt Wallace Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Luster
A D
AD
Ravetch
J V
JV
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D007371:Interferon-gamma