NEUROGENIC INFLAMMATION, VASCULAR-PERMEABILITY, AND MAST-CELLS - CAPSAICIN DESENSITIZATION FAILS TO INFLUENCE IGE-ANTI-DNP INDUCED VASCULAR-PERMEABILITY IN RAT AIRWAYS

Mast cells and neuropeptide-containing nerves occur in close proximity throughout the mucosa. The vasodilation that characteristically occurs after mast cell mediator release in skin is dependent upon sensory nerve activation with neuropeptide release. It was therefore of interest to examine the relationship between antigen-induced mast cell activation, vascular permeability, and the influence of capsaicin-sensitive sensory nerves in the airways. To examine this question, capsaicin was administered systemically and the 'desensitization' of the animals to topical capsaicin confirmed. Thereafter, capsaicin-desensitized animals were studied to see if mast cell mediator-induced vascular permeability was affected. Plasma protein extravasation (PPE) was induced in Sprague-Dawley rats by intratracheal infusion of capsaicin or by intratracheal infusion of mouse serum albumin-dinitrophenol (MSA-DNP) after passive sensitization with IgE-anti-DNP. Leaking vessels in the airways were localized by using Monastral blue B, a macromolecular tracer. In the trachea, leaking vessels were predominantly located in the anterior wall after capsaicin challenge and in the posterior wall with antigen challenge. PPE was quantified by preinjecting animals with 125I-labeled BSA and expressed as μl of plasma deposited in the trachea, bronchi, lungs, and tracheobronchial lavage (TBL). Within one minute after challenge, concentrations of capsaicin greater than 10-7 M significantly increased PPE in trachea and bronchial wall (+160% and +175% above control, respectively, with 10-5 M). PPE was also observed in the trachea and bronchi after antigen challenge in animals passively sensitized with IgE-anti-DNP (+200% and +153%, respectively). With both stimuli, concomitant exudation of plasma proteins into the airway lumen was observed as reflected by an increase in 125I-labeled BSA, in total protein, in endogenous albumin, and in the albumin/total protein ratio in the TBL. Systemic capsaicin pretreatment dramatically reduced the capacity of topically applied capsaicin to cause PPE in the airways (-90% in the trachea). In contrast, PPE induced in the airway or skin by antigen challenge was not affected by capsaicin desensitization. These results indicate that while both sensory nerve stimulation and mast cell activation can induce PPE, the vascular protein leakage induced by antigen challenge is independent of sensory nerve participation.