Mast Cell-Deficient KitW-sh Mice Develop House Dust Mite-Induced Lung Inflammation despite Impaired Eosinophil Recruitment

Abstract

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 Kit^w-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. Kit^w-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, Kit^w-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 Kit^w-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 Kit^w-sh mice display a selective impairment of eosinophil recruitment without differences in other features of allergic inflammation.

Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

“…Although the mechanisms of tryptase-induced transmigration of eosinophils are not completely understood, some experimental studies leave no doubt about the involvement of tryptase in such processes. Decreased eosinophil recruitment to tissues is observed in mast cell-deficient mice (de Boer et al 2014), as well as in experimental models where the PAR2 receptor was blocked (Hyun et al 2008;Matos et al 2013). Moreover, the positive correlation observed in this study between numbers of tryptase-IR mast cells and eosinophils could be also interpreted as evidence for the role of tryptase in eosinophil survival.…”

General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation

“…The HDM model used here is characterized by allergic inflammation eventually leading to pulmonary pathological features such as perivascular inflammation, interstitial inflammation, peribronchitis and oedema [17][18][19]. Using a semiquantitative scoring system to quantify lung pathology as a result of HDM exposure, we found that MyD88KO mice developed significantly less lung inflammation compared to control mice ( Fig.…”

Birch pollen‐specific subcutaneous immunotherapy reduces ILC2 frequency but does not suppress IL‐33 in mice

“…Tryptase activity was determined in BALF as described before . In short, 10 μL 6‐mmol/L chromogenic tryptase substrate S‐2288 (Chromogenix Instrumentation Laboratory, Milan, Italy) was added to 70 μL 57 mmol/L Tris‐HCl (pH 8.3) in a 96‐well microtiter plate.…”