Pentraxins and Fc receptors

Pentraxins are innate pattern recognition molecules whose major function is to bind microbial pathogens or cellular debris during infection and inflammation and, by doing so, contribute to the clearance of necrotic cells as well as pathogens through complement activations. Fc receptors are the cellular mediators of antibody functions. Although conceptually separated, both pentraxins and antibodies are important factors in controlling acute and chronic inflammation and infections. In recent years, increasing experimental evidence suggests a direct link between the innate pentraxins and humoral Fc receptors. Specifically, both human and mouse pentraxins recognize major forms of Fc receptors in solution and on cell surfaces with affinities similar to antibodies binding to their low affinity Fc receptors. Like immune complex, pentraxin aggregation and opsonization of pathogen result in Fc receptor and macrophage activation. The recently published crystal structure of human serum amyloid P (SAP) in complex with FcγRIIA further illustrated similarities to antibody recognition. These recent findings implicate a much broader role than complement activation for pentraxins in immunity. This review summarizes the structural and functional work that bridge the innate pentraxins and the adaptive Fc receptor functions. In many ways, pentraxins can be regarded as innate antibodies.