Neural-immune interactions in the airway wall

The hypothesis underlying our studies is that immunological stimulation of immune cells in the lungs results in alterations in the neurophysiology of the airways. One area in which nerve-immune interactions may be particularly relevant is in allergic disease. We are characterizing the neuronal consequences of the immediate hypersensitivity reaction in the guinea pig isolated airway. Animals are actively or passively sensitized such that subsequent antigen challenge in vivo results in mast cell activation and inflammatory mediator production. The mediator release in turn results in significant changes in the afferent and efferent neuronal control of the airway. The afferent innervation of the guinea pig trachea is derived from neurons situated in either the nodose or jugular vagal sensory ganglia. Along with our German colleagues (Wolfgang Kummer and Axel Fisher et al.). We have demonstrated that the anatomical and physiological phenotype of the afferent fiber innervation of the airway is dependent on which ganglion the neuron is located. The nerve fibers projecting to the airway from the nodose ganglion are primarily neuropeptide-negative, mechanically-sensitive, ehemoinsensitive, rapidly adapting Aθ fibers. By contrast, the jugular neurons project neuropeptide-positive C-fibers and neuropeptidenegative Aθ fibers to the airways. Regardless of their conduction velocity, jugular neurons are chemosensitive, less mechanically sensitive and adapt more slowly to suprathreshold stimulation than nodose fibers. Dr. Kummer and colleagues noted that within 1 day of antigen challenge in vivo, there is a 5-fold increase in the neuropeptide content in the lungs, Messenger RNA analysis suggests that antigen challenge induces nodose neurons, which are normally neuropeptide-negative Aθ fibers, to synthesize tachykinins. In addition to this neuroplasticity in response to antigen challenge, we have found enhanced excitability of airway nerve endings. On average, the sensitivity to mechanical stimulation of airway afferent nerve endings is incrased 5-fold subsequent to antigen exposure. The efferent innervation of the airways is also altered by antigen challenge. Immunological stimulation of mast cells leads to substantive increases in the efficacy of synaptic neurotransmission at the level of the local parasympathetic ganglia, and to enhanced efferent function of tachykinergic innervation in the airway.