Function and regulation of a murine macrophage-specific IgG Fc receptor, Fc gamma R-alpha.

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Abstract
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 cell lines exhibited increased receptor levels after IFN-.gamma. stimulation as measured by 125I-2.4G2 and ligand binding. In the P388D1 cells were actively phagocytic. In the presence of IFN-.GAMMA., however, RAW 264.7 and J7774a 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.