Allergen challenge-induced entry of α2-macroglobulin and tryptase into human nasal and bronchial airways☆,☆☆,★,★★
Section snippets
Subjects
Four women and four men, with a mean age of 35 years (range, 21 to 46 years), were enrolled in the study. They had a history of tree or grass pollen-induced rhinitis, recurring dry cough during the pollen season interpreted as slight bronchospasm, a positive skin prick test response to birch or timothy pollen, and increased levels of specific IgE antibodies in the blood as determined by RAST (Table I). Six of the patients (nos. 1, 2, 3, 5, 6, and 8) were free of symptoms and were not taking any
BAL fluid analysis
BAL fluid recovery (mean ± SEM) was 30.8% ± 4.1% (Cmean = mean of C1 and C2) and 33.7% ± 4.3% (Amean = mean of A1 and A2). BAL fluid levels (Cmean and Amean) of albumin, α2-macroglobulin, and tryptase are presented in Fig. 1. All BAL fluid samples were processed for analysis. The levels of albumin and α2-macroglobulin were clearly above the detection limits of the assays in all samples. Tryptase was demonstrated in all BAL samples from the allergen-challenged side and in half of the BAL samples
DISCUSSION
This study, which involved patients with allergy, demonstrates that topical allergen challenge of the airway mucosa of both nasal and bronchial passages produces increased levels of tryptase, a mast cell activation index, and increased levels of α2-macroglobulin, which is a marker of mucosal exudation of bulk plasma. The NAL technique revealed highly significant co-exudation of albumin. In sharp contrast, the BAL fluid levels of albumin did not differ between challenge and control conditions.
Acknowledgements
We thank Christina Larsson, RN, and Margita Dahl, RN, of the Department of Thoracic Medicine, Karolinska Hospital, Stockholm, for assistance with the nasal challenge procedures; Elsie Gerne, Birgitta Hörling, and Ulli Klaile-Hammarberg of the Department of Respiratory and Allergic Diseases, Huddinge University Hospital, for their professional assistance with the bronchial challenge procedures; and Parvesh Masson, PhD, of the Department of Bioanalysis, Astra Draco, Lund, for performing the
References (30)
Role of plasma exudation in asthmatic airways
Lancet
(1986)- et al.
Inflammatory passage of plasma macromolecules into airway wall and lumen
Pulm Pharmacol
(1989) - et al.
Fibrinogen and albumin on the surface of allergen- and histamine-exposed human nasal mucosa [Abstract]
J ALLERGY CLIN IMMUNOL
(1991) - et al.
Seasonal increase of bronchial reactivity in allergic rhinitis
J ALLERGY CLIN IMMUNOL
(1987) - et al.
A new radioimmunoassay for human mast cell tryptase using monoclonal antibodies
J Immunol Methods
(1991) - et al.
Microcirculation-derived factors in epithelial repair in vivo
Microvasc Res
(1994) Interactions between cytokines and α2-macroglobulin
Immunol Today
(1990)- et al.
The use of the nose to study the inflammatory response of the respiratory tract [Editorial]
Thorax
(1992) - et al.
Inflammatory leakage of macromolecules from the vascular compartment into the tracheal lumen
Acta Physiol Stand
(1986) - et al.
Histamine-induced airway mucosal exudation of bulk plasma and plasma-derived mediators is not inhibited by intravenous bronchodilators
Eur J Clin Pharmacol
(1994)
Allergen, bradykinin, and capsaicin increase outward but not inward macromolecular permeability of guinea-pig tracheobronchial mucosa
Clin Exp Allergy
Absorption of 51Cr-EDTA across the human nasal mucosa in the presence of topical histamine
Thorax
Effects of histamine, ethanol, and a detergent on exudation and absorption across guinea pig airway mucosa in vivo
Thorax
Subepithelial hydrostatic pressure may regulate plasma exudation across the mucosa
Int Arch Allergy Appl Immunol
Asymmetrical effects of increases in hydrostatic pressure on macromolecular movement across the airway mucosa. A study in guinea-pig tracheal tube preparations
Clin Exp Allergy
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From athe Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Lund; bthe Department for Respiratory and Allergic Diseases, University Hospital, Huddinge; cthe Department of Bioanalysis, Astra-Draco, Lund; and dthe Department of Clinical Pharmacology, University Hospital, Lund.
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Supported by grants from the Swedish Medical Research Council (project 8308), Konsul Th. C. Bergh's Foundation, the Swedish Association against Asthma and Allergy, and the Swedish Heart-Lung Foundation.
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Reprint requests: Carl G.A. Persson, PhD, Department of Clinical Pharmacology, University Hospital, S-221 85 Lund, Sweden.
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