Background: Mast cells are implicated in allergic and innate immune responses in asthma, although their role in models using an allergen relevant for human disease is incompletely understood. House dust mite (HDM) allergy is common in asthma patients. Our aim was to investigate the role of mast cells in HDM-induced allergic lung inflammation. Methods: Wild-type (Wt) and mast cell-deficient Kitw-sh mice on a C57BL/6 background were repetitively exposed to HDM via the airways. Results: HDM challenge resulted in a rise in tryptase activity in bronchoalveolar lavage fluid (BALF) of Wt mice, indicative of mast cell activation. Kitw-sh mice showed a strongly attenuated HDM- induced recruitment of eosinophils in BALF and lung tissue, accompanied by reduced pulmonary levels of the eosinophil chemoattractant eotaxin. Remarkably, Kitw-sh mice demonstrated an unaltered capacity to develop lung pathology and increased mucus production in response to HDM. The increased plasma IgE in response to HDM in Wt mice was absent in Kitw-sh mice. Conclusion: These data contrast with previous reports on the role of mast cells in models using ovalbumin as allergen in that C57BL/6 Kitw-sh mice display a selective impairment of eosinophil recruitment without differences in other features of allergic inflammation.

1.
Braman SS: The global burden of asthma. Chest 2006;130:4S-12S.
[PubMed]
2.
Murphy DM, O'Byrne PM: Recent advances in the pathophysiology of asthma. Chest 2010;137:1417-1426.
[PubMed]
3.
Gregory LG, Lloyd CM: Orchestrating house dust mite-associated allergy in the lung. Trends Immunol 2011;32:402-411.
[PubMed]
4.
Nelson RP Jr, DiNicolo R, Fernandez-Caldas E, Seleznick MJ, Lockey RF, Good RA: Allergen-specific IgE levels and mite allergen exposure in children with acute asthma first seen in an emergency department and in nonasthmatic control subjects. J Allergy Clin Immunol 1996;98:258-263.
[PubMed]
5.
Lodge CJ, Lowe AJ, Gurrin LC, Hill DJ, Hosking CS, Khalafzai RU, Hopper JL, Matheson MC, Abramson MJ, Allen KJ, Dharmage SC: House dust mite sensitization in toddlers predicts current wheeze at age 12 years. J Allergy Clin Immunol 2011;128:782-788.e9.
[PubMed]
6.
Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID: Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med 2002;346:1699-1705.
[PubMed]
7.
Wardlaw AJ, Brightling CE, Green R, Woltmann G, Bradding P, Pavord ID: New insights into the relationship between airway inflammation and asthma. Clin Sci (Lond) 2002;103:201-211.
[PubMed]
8.
Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M: Mast cells as ‘tunable' effector and immunoregulatory cells: recent advances. Annu Rev Immunol 2005;23:749-786.
[PubMed]
9.
Lorentz A, Schwengberg S, Sellge G, Manns MP, Bischoff SC: Human intestinal mast cells are capable of producing different cytokine profiles: role of IgE receptor cross-linking and IL-4. J Immunol 2000;164:43-48.
[PubMed]
10.
Kalesnikoff J, Galli SJ: New developments in mast cell biology. Nat Immunol 2008;9:1215-1223.
[PubMed]
11.
Chodaczek G, Bacsi A, Dharajiya N, Sur S, Hazra TK, Boldogh I: Ragweed pollen-mediated IgE-independent release of biogenic amines from mast cells via induction of mitochondrial dysfunction. Mol Immunol 2009;46:2505-2514.
[PubMed]
12.
de Boer JD, Majoor CJ, van 't Veer C, Bel EHD, van der Poll T: Asthma and coagulation. Blood 2012;119:3236-3244.
[PubMed]
13.
Kirshenbaum AS, Goff JP, Kessler SW, Mican JM, Zsebo KM, Metcalfe DD: Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells. J Immunol 1992;148:772-777.
[PubMed]
14.
Grimbaldeston MA, Chen CC, Piliponsky AM, Tsai M, Tam SY, Galli SJ: Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am J Pathol 2005;167:835-848.
[PubMed]
15.
Lyon MF, Glenister PH: A new allele sash (Wsh) at the W-locus and a spontaneous recessive lethal in mice. Genet Res 1982;39:315-322.
[PubMed]
16.
Jacquet A: The role of innate immunity activation in house dust mite allergy. Trends Mol Med 2011;17:604-611.
[PubMed]
17.
De Boer J, Roelofs JJ, de Vos AF, de Beer R, Schouten M, Hommes TJ, Hoogendijk AJ, de Boer OJ, Stroo I, van der Zee JS, Veer CV, van der Poll T: Lipopolysaccharide inhibits Th2 lung inflammation induced by house dust mite allergens in mice. Am J Respir Cell Mol Biol 2013;48:382-389.
[PubMed]
18.
Ishizaki M, Tanaka H, Kajiwara D, Toyohara T, Wakahara K, Inagaki N, Nagai H: Nafamostat mesilate, a potent serine protease inhibitor, inhibits airway eosinophilic inflammation and airway epithelial remodeling in a murine model of allergic asthma. J Pharmacol Sci 2008;108:355-363.
[PubMed]
19.
Payne V, Kam PC: Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia 2004;59:695-703.
[PubMed]
20.
Wardlaw AJ: Molecular basis for selective eosinophil trafficking in asthma: a multistep paradigm. J Allergy Clin Immunol 1999;104:917-926.
[PubMed]
21.
Dent G, Hadjicharalambous C, Yoshikawa T, Handy RL, Powell J, Anderson IK, Louis R, Davies DE, Djukanovic R: Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum. Am J Respir Crit Care Med 2004;169:1110-1117.
[PubMed]
22.
Kung TT, Stelts D, Zurcher JA, Jones H, Umland SP, Kreutner W, Egan RW, Chapman RW: Mast cells modulate allergic pulmonary eosinophilia in mice. Am J Respir Cell Mol Biol 1995;12:404-409.
[PubMed]
23.
Reuter S, Dehzad N, Martin H, Heinz A, Castor T, Sudowe S, Reske-Kunz AB, Stassen M, Buhl R, Taube C: Mast cells induce migration of dendritic cells in a murine model of acute allergic airway disease. Int Arch Allergy Immunol 2010;151:214-222.
[PubMed]
24.
Herrerias A, Torres R, Serra M, Marco A, Roca-Ferrer J, Picado C, de Mora F: Subcutaneous prostaglandin E2 restrains airway mast cell activity in vivo and reduces lung eosinophilia and Th2 cytokine overproduction in house dust mite-sensitive mice. Int Arch Allergy Immunol 2009;149:323-332.
[PubMed]
25.
Holgate ST: Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches? J Allergy Clin Immunol 2011;128:495-505.
[PubMed]
26.
Post S, Nawijn MC, Hackett TL, Baranowska M, Gras R, van Oosterhout AJ, Heijink IH: The composition of house dust mite is critical for mucosal barrier dysfunction and allergic sensitisation. Thorax 2012;67:488-495.
[PubMed]
27.
Yu M, Tsai M, Tam SY, Jones C, Zehnder J, Galli SJ: Mast cells can promote the development of multiple features of chronic asthma in mice. J Clin Invest 2006;116:1633-1641.
[PubMed]
28.
Spellberg B, Edwards JE Jr: Type 1/type 2 immunity in infectious diseases. Clin Infect Dis 2001;32:76-102.
[PubMed]
29.
Becker M, Reuter S, Friedrich P, Doener F, Michel A, Bopp T, Klein M, Schmitt E, Schild H, Radsak MP, Echtenacher B, Taube C, Stassen M: Genetic variation determines mast cell functions in experimental asthma. J Immunol 2011;186:7225-7231.
[PubMed]
30.
Hammad H, Chieppa M, Perros F, Willart MA, Germain RN, Lambrecht BN: House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 2009;15:410-416.
[PubMed]
31.
Wan H, Winton HL, Soeller C, Tovey ER, Gruenert DC, Thompson PJ, Stewart GA, Taylor GW, Garrod DR, Cannell MB, Robinson C: Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest 1999;104:123-133.
[PubMed]
32.
Wan H, Winton HL, Soeller C, Taylor GW, Gruenert DC, Thompson PJ, Cannell MB, Stewart GA, Garrod DR, Robinson C: The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus. Clin Exp Allergy 2001;31:279-294.
[PubMed]
33.
Cho HJ, Lee HJ, Kim SC, Kim K, Kim YS, Kim CH, Lee JG, Yoon JH, Choi JY: Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract. J Allergy Clin Immunol 2012;129:529-535.
[PubMed]
34.
Lindsey JY, Ganguly K, Brass DM, Li Z, Potts EN, Degan S, Chen H, Brockway B, Abraham SN, Berndt A, Stripp BR, Foster WM, Leikauf GD, Schulz H, Hollingsworth JW: C-kit is essential for alveolar maintenance and protection from emphysema-like disease in mice. Am J Respir Crit Care Med 2011;183:1644-1652.
[PubMed]
35.
Coyle AJ, Wagner K, Bertrand C, Tsuyuki S, Bews J, Heusser C: Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: inhibition by a non-anaphylactogenic anti-IgE antibody. J Exp Med 1996;183:1303-1310.
[PubMed]
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