Antigen-induced mast cell expansion and bronchoconstriction in a mouse model of asthma

Abstract

Lung mastocytosis and antigen-induced bronchoconstriction are common features in allergic asthmatics. It is therefore important that animal models of asthma show similar features of mast cell inflammation and reactivity to inhaled allergen. We hypothesized that house dust mite (HDM) would induce mastocytosis in the lung and that inhalation of HDM would trigger bronchoconstriction. Mice were sensitized with intranasal HDM extract, and the acute response to nebulized HDM or the mast cell degranulating compound 48/80 was measured with respiratory input impedance. Using the constant-phase model we calculated Newtonian resistance (Rn) reflecting the conducting airways, tissue dampening (G), and lung elastance (H). Bronchoalveolar lavage fluid was analyzed for mouse mast cell protease-1 (mMCP-1). Lung tissue was analyzed for cytokines, histamine, and α-smooth muscle actin (α-SMA), and histological slides were stained for mast cells. HDM significantly increased Rn but H and G remained unchanged. HDM significantly expanded mast cells compared with control mice; at the same time mMCP-1, α-SMA, Th2 cytokines, and histamine were significantly increased. Compound 48/80 inhalation caused bronchoconstriction and mMCP-1 elevation similarly to HDM inhalation. Bronchoconstriction was eliminated in mast cell-deficient mice. We found that antigen-induced acute bronchoconstriction has a distinct phenotype in mice. HDM sensitization caused lung mastocytosis, and we conclude that inhalation of HDM caused degranulation of mast cells leading to an acute bronchoconstriction without affecting the lung periphery and that mast cell-derived mediators are responsible for the development of the HDM-induced bronchoconstriction in this model.

Vitamin E Isoform γ-Tocotrienol Downregulates House Dust Mite–Induced Asthma

“…IgE-mediated mast cell degranulation is necessary for AHR by producing mediators, including IL-13, IL-17, IL-33, and histamine (31,44 (3,45). g-Tocotrienol was able to impede HDM-induced AHR by abrogating proinflammatory cytokines and serum IgE levels, as well as neutralizing oxidative stress and restoring antioxidant defenses, probably via inhibition of NF-kB activity and promotion of nuclear Nrf2 level.…”

“…IL-4, IL-5, IL-13, IL-17, IL-33, and TNF-a have all been shown to promote MUC5AC expression and goblet cell hyperplasia, and MUC5AC gene expression hinges on the transcriptional activity of NF-kB (29). IL-4 and IL-13 induce B cells to undergo isotype class switching to IgE production (30), and IgE cross-linking with FcεRI on mast cells leads to mast cell degranulation and bronchoconstriction (31). IL-10 plays a central role in potentiating regulatory T cell function and acts as an antiinflammatory cytokine in asthma (32).…”

Effects of JNJ-40929837, a leukotriene A4 hydrolase inhibitor, in a bronchial allergen challenge model of asthma

“…Moreover, JNJ-40929837 did not attenuate postBAC worsening of airway reactivity. Although specialized techniques such as barometric whole-body plethysmography and increases in enhanced pause [16], low-frequency forced oscillation [17] and respiratory input impedance [18] were not used to study allergeninduced bronchoconstriction in our murine models of LTB 4 inhibition, the failure of reduced LTB 4 production to attenuate the EAR and LAR following human BAC due to the absence of significant effects of JNJ-40929837 on sputum cell counts and airway reactivity, is perhaps not unexpected.…”

Análise da aplicação do modelo de fase constante na avaliação da mecânica respiratória em animais durante broncoconstrição.

“…Em especial os modelos no domínio da frequência, como o de fase constante (BATES, 2009;HANTOS et al, 1992;MORIYA;MORAES;THAMRIN et al, 2004 Um dos momentos em que estas condições não são apresentadas é durante a aplicação de broncoconstritores, prática amplamente utilizada a fim de estudar a inflamação pulmonar (LI et al, 2014), asma ou em outros modelos animais (SANTOS et al, 2014). A broncoconstrição, principalmente a broncoconstrição severa, acarreta: 1) alterações em propriedades intrínsecas ao pulmão;…”

“…Por fim, a quinta medida foi menor que a décima quinta medida. A grande maioria da literatura existente, que utiliza avaliação da mecânica respiratória em murinos durante curvas dose-resposta à MCh, apresenta somente os valores dos parâmetros do modelo de fase constante referentes aos picos de resistência newtoniana e omitem os valores de adequação do modelo de fase constante aos dados experimentais (COD) (ARANTES-COSTA et al, 2002;GOMES et al, 2000;JOHNSTON et al, 2008;LI et al, 2014;LIMJUNYAWONG;HORTON, 2014 Contudo, a intenção deste trabalho não é encontrar uma variável que substitua em todas as nuances um parâmetro modelado e sim descrever seus comportamentos.…”