title: IgE-challenged human lung mast cells excite vagal sensory neurons in vitro.
abstract: Substances released from immunoglobin (Ig) E-stimulated mast cells are likely to be among the chemical mediators responsible for changes in the vagal component of airway reactivity. We have attempted to identify a direct role for mast cell mediators in the control of visceral afferent excitability by examining intracellular electrophysiological changes in vagal neurons after application of extracts prepared from purified and IgE-stimulated human lung mast cells (HLMC). HLMC's, applied by superfusion or by focal pressure ejection from micropipettes, reversibly enhanced the excitability of a subpopulation of rabbit visceral sensory C-fiber neurons by 1) abolishing the slow Ca2+-dependent post-spike after hyperpolarization that uniquely resides in these neurons and controls their spike frequency, 2) depolarizing the cell membrane potential, and 3) increasing membrane input resistance. Control HLMC prepared by subjecting purified human lung mast cells to normal goat serum had no measurable affects on neuronal excitability. The immunologically released constituents responsible for these excitability changes are likely to be lipid mediators, because essentially all biological activity is extractable into an organic phase after methanol-chloroform solvent extraction of the HLMC preparations. These results provide the first unambiguous evidence that products released from immunologically challenged HLMC's directly affect visceral afferent nerve cell function.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, School of Medicine, University of Maryland, Baltimore.
authors.forename: R
authors.initials: R
authors.lastname: Greene
authors.forename: J
authors.initials: J
authors.lastname: Fowler
authors.forename: D
authors.initials: D
authors.lastname: MacGlashan
authors.forename: D
authors.initials: D
authors.lastname: Weinreich
mesh_terms: D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology*; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology*; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D007073:Immunoglobulin E