Direct action of immunoglobulin G on primary sensory neurons through Fc gamma receptor I

Abstract

Immunoglobulin G (IgG) binds specific antigens, and IgG-antigen complexes primarily activate immune cells and the complement system. These immune reactions are known to affect neural functions through the production and release of mediators such as cytokines. The high affinity IgG receptor FcgammaRI, but not the low affinity receptors FcgammaRII and FcgammaRIII, was expressed on the mouse dorsal root ganglion (DRG) neurons, especially small- or medium-sized neurons. IgG bound to DRG neurons and made a complex with antigen there. Ragweed pollen bound to nerve fibers in the skin of sensitized mouse in situ. The formation of IgG-ragweed pollen complex increased the concentration of Ca2+ ions in the DRG neurons. This increase was inhibited by a Ca2+ chelator, L- and N-type voltage-dependent Ca2+ channel blockers, and anti-FcgammaRI antibody. IgG-antigen complex released substance P from DRG neurons, which was inhibited by L- and N-type Ca2+ channel blockers. Thus, IgG and antigen combine on primary sensory neurons to directly activate them, which may be a novel type of immune-neuron linkage.