Asthma, rhinitis, other respiratory disorders
Demonstration of mast cell chemotactic activity in bronchoalveolar lavage fluid collected from asthmatic patients before and during pollen season,☆☆

https://doi.org/10.1067/mai.2000.104380Get rights and content

Abstract

Background: Mast cells are versatile effector cells of primary importance in asthma and airway inflammation. During inflammation mast cells accumulate in the bronchial epithelium. The mechanism for this increase in mast cell number has not been defined. Objectives: The aim of this study was to examine the presence of mast cell chemotactic activity in bronchoalveolar lavage (BAL) fluid taken before and at the end of 2 pollen seasons from patients with allergic asthma. Methods: To measure mast cell chemotactic activity, we used a modified Boyden chamber and the human mast cell line HMC-1 or in vitro–developed mast cells as responder cells. Results: A total of 27 patients were investigated, of which 8 exhibited mast cell chemotactic activity in their BAL fluid collected before season. A significant increase in the activity was found in 18 of 27 BAL fluids sampled at the end of the pollen season. No difference was found between patients treated with immunotherapy or placebo. The presence of stem cell factor could be detected in all BAL fluids analyzed. Blocking antibodies against stem cell factor or transforming growth factor-β partially blocked the activity in some of the BAL fluids. Treatment of the responder cells with pertussis toxin reduced the migratory activity in 13 of 14 BAL fluids collected during pollen season. Conclusion: This study demonstrates the presence of mast cell chemotactic activity in BAL fluids from patients with allergic asthma, with a significant increase in activity during pollen season. The major part of this activity consisted of factors mediating their effect through Gi-protein coupled receptors. This activity may be responsible for the mast cell accumulation in the intraepithelial layer seen in allergic asthmatic patients. (J Allergy Clin Immunol 2000;105:455-61.)

Section snippets

Patient selection

The BAL fluid was collected from patients participating in 2 independent birch pollen studies during the seasons of 1995 (series A) and 1997 (series B). All patients were nonsmokers. The diagnosis was based on history of allergic symptoms during birch pollen season confirmed by positive skin prick test with standardized birch extract (ALK, Hörsholm, Denmark) and positive CAP at least class 2 (CAP-system, Pharmacia and Upjohn Diagnostics, Uppsala, Sweden). They all had seasonal

Identification of mast cell chemotactic activity in BAL fluids

The presence of mast cell chemotactic activity in BAL fluids was analyzed with use of the human mast cell line HMC-1 or primary mast cells as a bioassay. Eight of 27 BAL fluids collected before pollen season exhibited mast cell chemotactic activity (Fig 1, A and B ).

. Mast cell chemotactic activity in BAL fluid. BAL fluids were collected either before(open bars) or during pollen season(filled bars) and tested on HMC-1 cells (A and B) or primary mast cells (C) (series A = 1995, series B = 1997).

DISCUSSION

We demonstrate for the first time that mast cell chemotactic activity is present in BAL fluids collected from asthmatic patients. Furthermore, activity was significantly higher in BAL fluids collected during the pollen season compared with those collected before the pollen season. Asthma is a complex disease characterized by an inflammatory response with leukocyte infiltrates, bronchial hyperresponsiveness, airway edema, and tissue remodeling.23 Mast cells are believed to be important for these

Acknowledgements

We thank Agneta Bretholtz, Yvonne Bäckberg, and Yvonne Andersson for technical assistance and Dr Steven Appleqvist for linguistic revision of the manuscript.

References (35)

  • L Enerbäck et al.

    Intraepithelial migration of nasal mucosal mast cells in hay fever

    Int Arch Allergy Immunol

    (1986)
  • M Okuda et al.

    Basophil leukocytes and mast cells in the nose

    Eur J Respir Dis

    (1983)
  • S Kawabori et al.

    Dynamics of mast cell degranulation in human allergic nasal epithelium after provocation with allergen

    Clin Allergy

    (1985)
  • PG Gibson et al.

    Intraepithelial mast cells in allergic and nonallergic asthma: assessment using bronchial brushings

    Am Rev Respir Dis

    (1993)
  • LA Laitinen et al.

    Airway mucosal inflammation even in patients with newly diagnosed asthma

    Am Rev Respir Dis

    (1993)
  • MP Borres et al.

    Metachromatic cells in nasal mucosa after allergen challenge

    Allergy

    (1990)
  • WJ Fokkens et al.

    Dynamics of mast cells in the nasal mucosa of patients with allergic rhinitis and non-allergic controls: a biopsy study

    Clin Exp Allergy

    (1992)
  • Cited by (28)

    • Transient targeting of phosphoinositide 3-kinase acts as a roadblock in mast cells' route to allergy

      2013, Journal of Allergy and Clinical Immunology
      Citation Excerpt :

      On SCF/c-Kit stimulation, PI3Kδ is required for migration and adhesion to HUVECs (partially also demonstrated by others).17,27 This might be of relevance in patients with neurofibromatosis (see Huang et al49 for references) or in asthmatic patients with increased SCF levels.50,51 The GPCR agonists adenosine, C5a, SDF-1α, and RANTES relayed their signals through PI3Kγ to adhesive and migratory processes of mast cells, which fits reports linking ligand/GPCR engagement with mast cell involvement in inflammatory conditions.52

    • Citreorosein, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, attenuates cyclooxygenase-2-dependent prostaglandin D <inf>2</inf> generation by blocking Akt and JNK pathways in mouse bone marrow-derived mast cells

      2012, Food and Chemical Toxicology
      Citation Excerpt :

      SCF is important for regulation of mast cell numbers in tissue, as well as being a potent chemotactic agent for mast cells (Meininger et al., 1992; Nilsson et al., 1994). SCF is also present in body fluids collected from patients with asthma, allergy, or rheumatoid arthritis and contributes, at least in part, to the mast cell chemotactic activity present in these fluids (Ceponis et al., 1998; Costa et al., 1996; Galli et al., 1993; Nilsson et al., 1998; Olsson et al., 2000). SCF in the presence of LPS, a bacterial endotoxin that stimulates a potent pro-inflammatory response, and IL-10, which is generally recognized as an anti-inflammatory cytokine but also has the capacity to promote mast cell proliferation and activation, induces the transcription and translation of COX-2 leading to delayed PGD2 generation (Moon et al., 1998; Murakami et al., 1995a, 1994).

    • Chemokine concentrations and mast cell chemotactic activity in BAL fluid in patients with eosinophilic bronchitis and asthma, and in normal control subjects

      2006, Chest
      Citation Excerpt :

      This may provide a plausible explanation for our inability to show mast cell migration toward BAL fluid from asthmatic subjects as we recruited subjects with mild asthma who had minimal symptoms and perhaps BAL fluid from asthmatic subjects may be chemotactic for mast cells only when the subjects have more active disease. Of note, the mast cell chemotactic activity of the asthmatic BAL fluid obtained during the pollen season in this previous report20 was increased 1.5-fold over that of the control subjects, which was similar to that observed in our subjects with eosinophilic bronchitis, suggesting that this degree of chemotaxis is likely to be biologically relevant. An alternative explanation for the differential effect on mast cell chemotaxis toward BAL fluid from subjects with asthma and eosinophilic bronchitis is that mast cell migration to the superficial airway may be a more prominent feature of eosinophilic bronchitis.

    • Stem cell factor stimulates the chemotaxis, integrin upregulation, and survival of human basophils

      2005, Journal of Allergy and Clinical Immunology
      Citation Excerpt :

      Genetic or pharmacologic inactivation of PI-3 kinase in mice inhibits the responses to SCF and protects them also against allergic inflammation.30 SCF is present and partially accounts for mast cell chemotactic activity in bronchoalveolar and nasal lavage fluid collected from atopic patients,31,32 hence suggesting a role for SCF also in human pathology. Although c-kit expression on basophils has been demonstrated,33 the role of SCF in basophil function has remained controversial: although some authors could demonstrate that SCF enhances basophil histamine release, others did not.33,34

    View all citing articles on Scopus

    Supported by the Swedish Asthma and Allergy Association, the Swedish Foundation for Health Care Sciences and Allergy Research, the Swedish Heart Lung Foundation, the Ollie and Elof Ericssons Foundation, and King Gustaf V’s 80-Years Foundation.

    ☆☆

    Reprint requests: Gunnar Nilsson, PhD, Department of Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden.

    View full text