Characterization of the Fc receptor for IgG on a human macrophage cell line, U937.

Since the U937 cell line expresses many characteristics of normal human monocytes and macrophages, we studied in detail its receptors for IgG by measuring direct binding and inhibition of binding of 16 radioiodinated human myeloma proteins representative of the 4 subclasses. As with normal monocytes, IgG1 and IgG3 bound most efficiently (17.3 and 15.7% bound), IgG4 less readily (7.1% bound), and IgG2 least readily (0.6% bound). Scatchard plots of IgG1 binding showed approximately 18,000 binding sites/cell with Ka approximately 10(8) liter/mol. IgG1 binding was inhibited equally well by IgG1 and IgG3 (50% inhibition with 0.26 +/- 0.03 and 0.26 +/- 0.09 microgram, respectively). IgG4 inhibited less readily (0.68 +/- 0.12 microgram). Three IgG2 proteins were not inhibitory (115 +/- 59) but one IgG2 myeloma inhibited well (0.89 +/- 0.47). IgG Fc fragments inhibited IgG1 binding 1000-fold more efficiently than Fab fragments, IgM, and IgA. Reciprocal inhibition experiments gave no indication of multiple receptor sites of differing specificities. In situ, the IgG1 receptor was resistant to proteases. The data suggest that the U937 Fc receptor may be a useful model of human macrophage structure and function.