Current Allergy and Asthma Reports

, Volume 5, Issue 2, pp 130–135 | Cite as

The re-emergence of the mast cell as a pivotal cell in asthma pathogenesis

  • Christopher E. Brightling
  • Peter Bradding

Abstract

Asthma is characterized by variable airflow obstruction, airway hyperresponsiveness, and airway inflammation. Mast cells have long been thought to play a central role in asthma through their ability to release proinflammatory mediators, but this role has been questioned by the lack of efficacy of antihistamines and so-called mast cell-stabilizing drugs. Recent comparisons between the immunopathology of asthma and eosinophilic bronchitis have led to the re-emergence of the mast cell as a pivotal cell in asthma. Eosinophilic bronchitis is a condition in which patients present with chronic cough, and shares many of the inflammatory features associated with asthma, but without variable airflow obstruction or airway hyperresponsiveness. The only striking pathologic difference between these conditions is that, in asthma, the airway smooth muscle is infiltrated by mast cells. This suggests that interactions between mast cells and airway smooth muscle cells are critical for the development of the disordered airway physiology in asthma.

References and Recommended Reading

  1. 1.
    Wardlaw AJ, Brightling C, Green R, et al.: Eosinophils in asthma and other allergic diseases. Br Med Bull 2000, 56:985–1003.PubMedCrossRefGoogle Scholar
  2. 2.
    Robinson DS, Hamid Q, Ying S, et al.: Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992, 326:298–304.PubMedCrossRefGoogle Scholar
  3. 3.
    Djukanovic R, Wilson JW, Britten KM, et al.: Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. Am Rev Respir Dis 1990, 142:863–871.PubMedGoogle Scholar
  4. 4.
    Leckie MJ, ten Brinke A, Khan J, et al.: Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet 2000, 356:2144–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS: Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003, 167:199–204.PubMedCrossRefGoogle Scholar
  6. 6.
    Green RH, Brightling CE, Woltmann GW, et al.: Analysis of induced sputum in adults with asthma: identification of a subgroup with neutrophilic inhaled corticosteroid resistant disease. Thorax 2002, 57:875–879.PubMedCrossRefGoogle Scholar
  7. 7.
    Brightling CE, Ward R, Goh KL, et al.: Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med 1999, 160:406–410.PubMedGoogle Scholar
  8. 8.
    Gibson PG, Dolovich J, Denburg J, et al.: Chronic cough: eosinophilic bronchitis without asthma. Lancet 1989, 1:1346–1348.PubMedCrossRefGoogle Scholar
  9. 9.
    Brightling CE, Bradding P, Symon FA, et al.: Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med 2002, 346:1699–1705. Mast cell infiltration of the airway smooth muscle is a feature of asthma and not eosinophilic bronchitis or normal controls, suggesting that this may be a critical determinant of the asthma phenotype.PubMedCrossRefGoogle Scholar
  10. 10.
    Schwartz LB, Irani AM, Roller K, et al.: Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol 1987, 138:2611–2615.PubMedGoogle Scholar
  11. 11.
    MacGlashan DW Jr, Schleimer RP, Peters SP, et al.: Generation of leukotrienes by purified human lung mast cells. J Clin Invest 1982, 70:747–751.PubMedCrossRefGoogle Scholar
  12. 12.
    Bradding P, Roberts JA, Britten KM, et al.: Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 1994, 10:471–480.PubMedGoogle Scholar
  13. 13.
    Machado DC, Horton D, Harrop R, et al.: Potential allergens stimulate the release of mediators of the allergic response from cells of mast cell lineage in the absence of sensitization with antigen-specific IgE. Eur J Immunol 1996, 26:2972–2980.PubMedCrossRefGoogle Scholar
  14. 14.
    O’Donnell MC, Ackerman SJ, Gleich GJ, Thomas LL: Activation of basophil and mast cell histamine release by eosinophil granule major basic protein. J Exp Med 1983, 157:1981–1991.PubMedCrossRefGoogle Scholar
  15. 15.
    Banks JR, Kagey-Sobotka A, Lichtenstein LM, Eggleston PA: Spontaneous histamine release after exposure to hyperosmolar solutions. J Allergy Clin Immunol 1986, 78:51–57.PubMedCrossRefGoogle Scholar
  16. 16.
    Liu MC, Bleecker ER, Lichtenstein LM, et al.: Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma. Am Rev Respir Dis 1990, 142:126–132.PubMedGoogle Scholar
  17. 17.
    Sedgwick JB, Calhoun WJ, Gleich GJ, et al.: Immediate and late airway response of allergic rhinitis patients to segmental antigen challenge: characterization of eosinophil and mast cell mediators. Am Rev Respir Dis 1991, 144:1274–1281.PubMedGoogle Scholar
  18. 18.
    Church MK, Hiroi J: Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol. Br J Pharmacol 1987, 90:421–429.PubMedGoogle Scholar
  19. 19.
    Howarth PH, Durham SR, Lee TH, et al.: Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma. Am Rev Respir Dis 1985, 132:986–992.PubMedGoogle Scholar
  20. 20.
    Roquet A, Dahlen B, Kumlin M, et al.: Combined antagonism of leukotrienes and histamine produces predominant inhibition of allergen-induced early and late phase airway obstruction in asthmatics. Am J Respir Crit Care Med 1997, 155:1856–1863.PubMedGoogle Scholar
  21. 21.
    Carroll NG, Mutavdzic S, James AL: Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J 2002, 19:879–885.PubMedCrossRefGoogle Scholar
  22. 22.
    Pesci A, Foresi A, Bertorelli G, et al.: Histochemical characteristics and degranulation of mast cells in epithelium and lamina propria of bronchial biopsies from asthmatic and normal subjects. Am Rev Respir Dis 1993, 147:684–689.PubMedGoogle Scholar
  23. 23.
    Gibson PG, Allen CJ, Yang JP, et al.: Intraepithelial mast cells in allergic and nonallergic asthma: assessment using bronchial brushings. Am Rev Respir Dis 1993, 148:80–86.PubMedGoogle Scholar
  24. 24.
    Connell JT: Asthmatic deaths: role of the mast cell. JAMA 1971, 215:769–776.PubMedCrossRefGoogle Scholar
  25. 25.
    Carroll NG, Mutavdzic S, James AL: Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma. Thorax 2002, 57:677–682. Mast cells infiltrate the airway mucous glands in patients with asthma and the number of cells correlated with the degree of mucus plugging.PubMedCrossRefGoogle Scholar
  26. 26.
    Koshino T, Teshima S, Fukushima N, et al.: Identification of basophils by immunohistochemistry in the airways of post-mortem cases of fatal asthma. Clin Exp Allergy 1993, 23:919–925.PubMedCrossRefGoogle Scholar
  27. 27.
    Ammit AJ, Bekir SS, Johnson PR, et al.: Mast cell numbers are increased in the smooth muscle of human sensitized isolated bronchi. Am J Respir Crit Care Med 1997, 155:1123–1129.PubMedGoogle Scholar
  28. 28.
    Broide DH, Gleich GJ, Cuomo AJ, et al.: Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. J Allergy Clin Immunol 1991, 88:637–648.PubMedCrossRefGoogle Scholar
  29. 29.
    Casale TB, Wood D, Richerson HB: Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with methacholine bronchial hyperresponsiveness. J Clin Invest 1987, 79:1197–1203.PubMedGoogle Scholar
  30. 30.
    Wardlaw AJ, Dunnette S, Gleich GJ, et al.: Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma: relationship to bronchial hyperreactivity. Am Rev Respir Dis 1988, 137:62–69.PubMedGoogle Scholar
  31. 31.
    Brightling CE, Symon FA, Holgate ST, et al.: Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma. Clin Exp Allergy 2003, 33:1711–1716. Mast cells within the airway smooth muscle in asthma express IL-4 and IL-13.PubMedCrossRefGoogle Scholar
  32. 32.
    Swystun VA, Gordon JR, Davis EB, et al.: Mast cell tryptase release and asthmatic responses to allergen increase with regular use of salbutamol. J Allergy Clin Immunol 2000, 106:57–64.PubMedCrossRefGoogle Scholar
  33. 33.
    Djukanovic R, Wilson JW, Britten KM, et al.: Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis 1992, 145:669–674.PubMedGoogle Scholar
  34. 34.
    Djukanovic R, Wilson SJ, Kraft M, et al.: Effects of treatment with anti-immunoglobulin e antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med 2004, 170:583–593. Anti-IgE therapy has a marked, broad-spectrum anti-inflammatory effect.PubMedCrossRefGoogle Scholar
  35. 35.
    Milgrom H, Fick RB, Su JQ, et al.: Treatment of allergic asthma with monoclonal anti-IgE antibody. N Eng J Med 1999, 342:1966–1973.CrossRefGoogle Scholar
  36. 36.
    Busse WW, Corren J, Lanier BQ, et al.: Omalizumab, anti-IgE recombinant humanised monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001, 108:184–190.PubMedCrossRefGoogle Scholar
  37. 37.
    Boulet LP, Chapman KR, Cote J, et al.: Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med 1997, 155:1835–1840.PubMedGoogle Scholar
  38. 38.
    Berger P, Girodet PO, Begueret H, et al.: Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J 2003, 17:2139–2141. Evidence to support mast cell migration to stimulated airway smooth muscle.PubMedGoogle Scholar
  39. 39.
    Hirst SJ, Hallsworth MP, Peng Q, Lee TH: Selective induction of eotaxin release by interleukin-13 or interleukin-4 in human airway smooth muscle cells is synergistic with interleukin-1beta and is mediated by the interleukin-4 receptor alpha-chain. Am J Respir Crit Care Med 2002, 165:1161–1171.PubMedGoogle Scholar
  40. 40.
    John M, Au BT, Jose PJ, et al.: Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th-2 cytokines and corticosteroids. Am J Respir Cell Mol Biol 1998, 18:84–90.PubMedGoogle Scholar
  41. 41.
    Brightling CE, Ammitt AJ, Berger P, et al.: CXCL10 (IP-10) is a novel mast cell chemokine and is released by asthmatic airway smooth muscle. Am J Respir Crit Care Med 2004, 169:A569.Google Scholar
  42. 42.
    Broekelmann TJ, Limper AH, Colby TV, et al.: Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci 1991, 88:6642–6646.PubMedCrossRefGoogle Scholar
  43. 43.
    Brown JK, Jones CA, Rooney LA, et al.: Tryptase’s potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions. Am J Physiol Lung Cell Mol Physiol 2002, 282:L197-L206. Tryptase is a mitogen for human airway smooth muscle.PubMedGoogle Scholar
  44. 44.
    Panettieri RA, Tan EM, Ciocca V, et al.: Effects of LTD4 on human airway smooth muscle cell proliferation, matrix expression, and contraction in vitro: differential sensitivity to cysteinyl leukotriene receptor antagonists. Am J Respir Cell Mol Biol 1998, 19:453–461.PubMedGoogle Scholar
  45. 45.
    Rajah R, Nunn SE, Herrick DJ, et al.: Leukotriene D4 induces MMP-1, which functions as an IGFBP protease in human airway smooth muscle cells. Am J Physiol 1996, 271:L1014-L1022.PubMedGoogle Scholar
  46. 46.
    Laporte JC, Moore PE, Baraldo S, et al.: Direct effects of interleukin-13 on signaling pathways for physiological responses in cultured human airway smooth muscle cells. Am J Respir Crit Care Med 2001, 164:141–148.PubMedGoogle Scholar
  47. 47.
    Grunstein MM, Hakonarson H, Leiter J, et al.: IL-13 dependent autocrine signalling mediates altered responsiveness of IgEsensitized airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 2002, 282:520–528.Google Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Christopher E. Brightling
    • 1
  • Peter Bradding
    • 1
  1. 1.Institute for Lung Health, Department of Respiratory MedicineUniversity of Leicester and Warwick Medical School, University Hospitals of LeicesterLeicesterUK

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