Cross‐linking of Both Types of IgG Fc Receptors, FcγyRI and FcγyRII, Enhances Intracellular Free Ca2+ in the Monocytic Cell Line U937

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Abstract
We have studied the effects of Fc receptor triggering on the free cytosolic Ca2+ concentration, [Ca2+]i, in U937. These cells express two types of IgG Fc receptors, FcγRI and FcγRII. Binding of several anti‐FcγRI and anti‐FcγRII mouse monoclonal antibodies (MoAb) to Quin2‐ or Indo‐I‐loaded U937 cells had no direct effect on [Ca2+]i. After addition of a bridging anti‐mouse Ig antibody however, transient increases in [Ca2+]i were observed for both types of FcγR. One of the anti‐FcγRII MoAb, CIKM5, was exceptional in that it could induce Ca2+ increases in U937 cells by itself. Studies with F(ab′)2 fragments of CIK M5 revealed that this MoAb simultaneously binds to FcγRII, via both its Fab and Fc fragments, which might induce cross‐linking of two FcγRII molecules. One anti‐FcγRI MoAb, 197, a mouse (m)IgG2a antibody directed to an epitope outside the IgG‐binding region, remarkably also caused an immediate increase in [Ca2+]i, but only when added to U937 precultured with gamma interferon (IFN‐γ). FcγRI can bind monomeric human IgG as well as mIgG2a, and cross‐linking of cytophilic Ig induced an increase in [Ca2+]i. Our results show that [Ca2+]i increases can be induced only after cross‐linking of FcγR, either via anti‐FcγR MoAb or via Fc‐FcR interactions. Furthermore, we show that FcγR cross‐linking results in activation of the Ca2+/phosphatidylinositol (PI) signal transduction pathway.