FC-GAMMA RECEPTOR LIGAND INTERACTIONS ENHANCE MACROPHAGE GSIB4-BINDING ACTIVITY

Activated macrophages have an increased ability to bing the lectin Griffonia simplicifolia-IB4 (GSIB4). Since macrophages readily use the Fc-receptor (FcR) during several immunologic and inflammatory processes, it is important to determine whether interactions with this moiety affect GSIB4-binding ability. Peritoneal macrophages cultured in vitro with Fc fragments of immunoglobulin G (IgG), whole IgG, or heat-aggregated IgG demonstrate an increase in this function. Conversely, treatment of macrophages with (Fab')2 fractions alone has no direct affect on this activity. Although the GSIB4-binding response is minimally expressed by normal macrophages, it is more markedly apparent on macrophages from LPS-treated animals. In both cases, however, pretrypsinization of the cells renders them refractory to IgG-mediated induction of the GSIB-binding response. Moreover, macrophages cultured independently with IgG subclasses, 1, 2a or 3 demonstrate that the magnitude of their response to this signal is directly associated with the type of subclass used. Although each subclass enhanced the response, in this study interactions with IgG(2a) produced the best results. Overall, however, the greatest GSIB4-binding activity is generated when FcRs are crosslinked by aggregated IgG rather than simply bound by independent monomeric interactions at the FcRs. This suggests that the event of appropriately interacting with the FcRc ampliflies the GSIB4-binding function. Such a mechanism could play a key role in coordinating the humoral, cell-mediated , and innate responses of the immune system.