Fcγ receptor signaling in response to soluble versus immobilized IgG

Fcγ receptors present on monocytes and macrophages clear pathogens engaged by antibodies through the process of endocytosis. Upon being clustered by immune complexes, Fcγ receptors initiate signaling that lead to cellular activation and cytokine secretion, processes that are likely terminated upon receptor internalization and subsequent degradation. In many disease states, however, Fcγ receptors encounter their ligands in the tissue deposited form that cannot be readily internalized. In this project, we examined kinetics of Erk 1/2 phosphorylation and TNF-α secretion in enriched human primary monocytes in response to stimulation of Fcγ receptors by soluble heat aggregated IgG or plastic surface-bound IgG, to mimic immune complexes and tissue-deposited IgG, respectively. Soluble aggregated IgG induced transient and robust signaling, leading to peak levels of phospho-Erk 1/2 by 15 minutes and TNF-α secretion by 1 hour, in contrast to surface-bound IgG, which caused sustained signaling lasting for hours, supporting the hypothesis that signal termination is dependent upon receptor internalization.M.Sc