title: Role of sensory innervation and mast cells in neurogenic plasma protein exudation into the airway lumen.
abstract: Neurogenic inflammation in the airways involves both mucosal oedema and plasma protein exudation into the airway lumen. We aimed to investigate the mechanism of exudation of plasma proteins into the airway lumen. Neurogenic inflammation was induced in anaesthetized Sprague-Dawley rats by electrical stimulation of both vagal nerves at 20 V, 10 Hz, 5 ms. Vascular permeability was measured as 125I-albumin extravasation into both the airway wall and tracheobronchial lavage fluid. Following vagal stimulation, tracheobronchial lavages were analysed for albumin, total protein, histamine, immunoreactive substance P (SP), and immunoreactive calcitonin gene-related peptide (CGRP). Vagal stimulation rapidly increased vascular permeability in the airway mucosa and induced exudation of plasma proteins into the tracheobronchial fluid. Pre-treatment with capsaicin inhibited both neurogenic vascular permeability and movement of albumin into the airway lumen. SP and CGRP were detectable in basal lavages (1.37+/-0.12 ng/mL and 2.17+/-0.21 ng/mL, respectively) and the concentration of SP fell by 43% following treatment with capsaicin. Following vagal stimulation, concentrations of both SP and CGRP decreased significantly. Although basal tracheobronchial lavages contained histamine, vagal stimulation did not increase the histamine concentration. These results indicate that both neurogenic vascular permeability and plasma protein exudation into the airway lumen results from activation of capsaicin-sensitive sensory nerves and the reaction is not associated with mast cell activation.
authors.affiliation: Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: M L
authors.initials: ML
authors.lastname: Kowalski
authors.forename: A
authors.initials: A
authors.lastname: Didier
authors.forename: J D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Y
authors.initials: Y
authors.lastname: Igarashi
authors.forename: M A
authors.initials: MA
authors.lastname: Kaliner
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001798:Blood Proteins / Q000032:analysis*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002211:Capsaicin / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005122:Exudates and Transudates / Q000737:chemistry / Q000187:drug effects; D006632:Histamine / Q000032:analysis; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000032:analysis*; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013373:Substance P / Q000032:analysis; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology*; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D001798:Blood Proteins; D009479:Neuropeptides; D013373:Substance P; D006632:Histamine; D002211:Capsaicin