Allergen challenge-induced entry of α2-macroglobulin and tryptase into human nasal and bronchial airways,☆☆,,★★

https://doi.org/10.1016/S0091-6749(95)70013-7Get rights and content

Abstract

Background: Microvascular-epithelial exudation of bulk plasma may characterize inflammatory airway diseases. This study compares the acute allergen challenge–induced mast cell and exudative responses in nasal and bronchial airways. The focus is on α2-macroglobulin as an index of luminal entry of plasma exudates. Methods: Separate nasal and bronchial allergen challenges were carried out outside the pollen season in eight patients with pollen-induced seasonal allergic rhinitis. The levels of different-sized plasma proteins (albumin molecular weight, 66,000 d and α2-macroglobulin molecular weight, 725,000 d) and tryptase were determined in pre- and postchallenge nasal lavage and bronchoalveolar lavage (BAL) fluids. Diluent and increasing doses of allergen were sprayed into the right nasal cavity, and each challenge was followed by a nasal lavage (volume, 15 ml) with a “nasal pool” device (recovery, >80%). Endobronchial allergen challenge (individual doses) and BAL (volume, 2 × 25 ml) were performed in a lobe bronchus through a fiberoptic bronchoscope (recovery, 30%). Saline challenge and BAL were carried out in the contralateral lung as control. Results: The levels of albumin, α2-macroglobulin, and tryptase increased dose-dependently in postchallenge nasal lavage fluids (p < 0.05) and correlated to nasal symptoms. In particular, albumin and α2-macroglobulin correlated (r = 0.98, p < 0.001). Both α2-macroglobulin and tryptase, but not albumin, were increased in BAL fluids from the allergen-challenged side (p < 0.05). Conclusion: Local allergen challenge causes luminal entry of tryptase and α2-macroglobulin in the nose and bronchi of patients with allergy. We suggest that mast cell and plasma exudation responses may be similar in human nasal and bronchial airways and that albumin levels (in BAL fluids) may not well reflect the exudation process in bronchial airways. (J ALLERGY CLIN IMMUNOL 1995;96:239-46.)

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)

  • I Erjefält et al.

    Allergen, bradykinin, and capsaicin increase outward but not inward macromolecular permeability of guinea-pig tracheobronchial mucosa

    Clin Exp Allergy

    (1991)
  • L Greiff et al.

    Absorption of 51Cr-EDTA across the human nasal mucosa in the presence of topical histamine

    Thorax

    (1991)
  • L Greiff et al.

    Effects of histamine, ethanol, and a detergent on exudation and absorption across guinea pig airway mucosa in vivo

    Thorax

    (1991)
  • CGA Persson et al.

    Subepithelial hydrostatic pressure may regulate plasma exudation across the mucosa

    Int Arch Allergy Appl Immunol

    (1990)
  • B Gustafsson et al.

    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

    (1991)
  • Cited by (53)

    • Airways exudation of plasma macromolecules: Innate defense, epithelial regeneration, and asthma

      2019, Journal of Allergy and Clinical Immunology
      Citation Excerpt :

      Effects of plasma exudation on the distribution of mucosal cell-derived molecules might need consideration in studies of airway samples. Although plasma exudation might be a common feature of asthma in general,42,116 the best evidence for occurrence of plasma exudation in asthmatic patients might emanate from studies of patients with severe eosinophilic42,117 or neutrophilic118 asthma and from studies in which asthmatic patients are challenged by insults/interventions known to worsen asthma: the common cold,45 allergen exposure,102 or a stepwise reduction in anti-inflammatory treatment.117,119 Plasma exudation indices might even be a dominating inflammatory index of worsening asthma.120

    • Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis

      2014, Journal of Allergy and Clinical Immunology
      Citation Excerpt :

      A2M is the only significantly increased antiproteinase in mucus from patients with allergic rhinitis with potential for inhibition of all 4 classes of proteinases (serine proteinases, cysteine proteinases, aspartic proteinases, and metalloproteinases). It traps the enzyme and decreases its proteolytic activity for high-weight substrates by hydrolyzing a thioester bond and covalent binding to the protease.38-41 Next to A2M, another proteinase inhibitor, SERPINA1, was significantly more abundant in patients with allergic rhinitis.

    • Lower respiratory tract complications during nasal provocation: Nonspecific stimulant or specific allergen?

      2007, Annals of Allergy, Asthma and Immunology
      Citation Excerpt :

      On the contrary, Jacobi et al16 detected increased histamine levels in nasal lavage with methacholine in patients with allergic rhinitis. Additionally, previous literature reports the presence of tryptase in nasal lavage after specific allergen challenge, but no similar data are available after methacholine.16-20 Therefore, nasal obstruction caused by methacholine is mediated by cholinergic receptors independent of mast cell degranulation.

    View all citing articles on Scopus

    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.

    ☆☆

    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.

    Reprint requests: Carl G.A. Persson, PhD, Department of Clinical Pharmacology, University Hospital, S-221 85 Lund, Sweden.

    ★★

    0091-6749/95 $3.00 + 0 1/1/63276

    View full text