Radiolabeled protein A from Staphylococcus aureus (SpA) injected i.v. into mice and rabbits forms a soluble [(IgG)2-(SpA)1]2 complex (Mr = 684 000) which is identical in composition to that formed by SpA in vitro with an equivalent amount or an excess of IgG. A soluble rabbit IgG-SpA complex injected into a mice or rabbits dissociates completely in vivo and a new complex is formed with the IgG of the recipient animal. The half-life of SpA administered to a mouse or a rabbit is therefore the half-life of the IgG-SpA complex formed in vivo. In mice and rabbits the half-life of the complexes formed is 9 and 30 h, respectively, whereas the half-life of rabbit IgG in these animals is 106 and 153 h, respectively. Fragment B of SpA (fSpA) reacts with IgG of mouse and rabbit and forms an (IgG)1-(fSpA)1 complex. Complexes of identical composition are formed if fSpA is injected i.v. into mice and rabbits. The half-life of the complexes in mice and rabbits are much shorter than those of the corresponding free IgG in these animals (up to 15 times). This result suggests that the binding of fSpA to the CH2 and the CH3 domains of IgG alters the function of the site, which controls the catabolism of IgG and is located in the CH2 domain. By contrast, fSpA does not change the Fc receptor-binding site of IgG, indicating that the Fc receptor site and the catabolic site are unrelated to each other.

Evidence is presented concerning the existence on mouse peritoneal macrophages of two separate and distinct Fc receptors, one for cytophilic monomeric IgG (mIgG) and the other for polymeric IgG. The latter Fc receptor recognizes both heat-aggregated IgG and antigen-complexed IgG. The major findings of our studies are: (a) the different susceptibility of the two Fc receptor types by pronase, trypsin or phospholipase C; (b) the independent modulation of these two binding sites on the cell membrane; (c) the inability of mIgG to inhibit the binding of particulate antigen-complexed IgG ligand; (d) the ability of mIgG molecules which are devoid of the cytophilic property to attach to the macrophage surface upon their polymerization induced by heating or antigen. The results are discussed in terms of "cytophilic" and "opsonic" Fc receptor types which may provide different functional abilities for normal macrophages.

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Mouse peritoneal macrophages were charged with IgG molecules in monomeric (mIgG), heat-aggregated (agIgG) or antigen-complexed (acIgG) form. Upon exposure to 37 degrees C, all bound IgG ligand types are redistributed on the cell surface due to the mobilization of their corresponding Fc receptor (FcR). The major findings regarding the fate of FcR on macrophages bearing IgG ligands are as follows: (a) the FcR involved in the binding of cytophilic molecules has a slow movement on the cell membrane and forms patches but never caps, while the opsonic type of FcR is rapidly capped; (b) the mobility of IgG-binding sites was temperature-dependent and was affected differently by sodium azide; this metabolic inhibitor enhances the disappearance of mIgG from the cell surface but decreases the capping and the disappearance of polymeric ligands; (c) both FcR types are probably ingested when complexed with specific ligand, and consequently, the rebinding of homologous IgG molecules is reduced, the clearing induced by agIgG or acIgG binding being much more extensive; and (d) cells cleared of their opsonic types of FcR are able to regenerate the receptor molecules with 8 h of incubation at 37 degrees C.

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