Ovalbumin‐sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation

Zosky, Graeme R.; Larcombe, Alexander N.; White, Olivia; Burchell, Jennifer; Jánosi, Tibor Z.; Hantos, Zoltán; Holt, Patrick G.; Sly, Peter D.; Turner, Debra J.

doi:10.1111/j.1365-2222.2007.02884.x

Cited by 65 publications

(57 citation statements)

References 43 publications

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“…findings correlate well with the asthma model reported by Zosky et al [29] . Sera from KO mice showed a similar level of IgE and a higher level of IgG1 compared to WT mice.…”

Section: Discussionsupporting

confidence: 82%

“…It was reported that OVA-sensitized mice are good models for airway hyperresponsiveness, but not for acute response to inhaled allergen after OVA challenge because of limited EPR and LPR in BALB/c mice [29] . In our study, airway hyperresponsiveness to MCh was successfully induced in both KO and WT mice, with the extent of increase significantly larger in KO mice than in WT mice.…”

Section: Discussionmentioning

confidence: 99%

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Deficiency in the Serum-Derived Hyaluronan-Associated Protein-Hyaluronan Complex Enhances Airway Hyperresponsiveness in a Murine Model of Asthma

Zhu

Zhuo

Kimata

et al. 2010

Int Arch Allergy Immunol

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phase responses were similar. Cell differentials of BALF showed an increased number of macrophages and neutrophils in KO mice. Furthermore, decreased concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1) were found in BALF from KO mice whereas the levels of Th1 and Th2 cytokines were not different from WT mice. Immunochemical study of the lung tissues revealed stronger staining of sTNFR1 in KO than in WT mice. Conclusions: Our results suggest that in this murine asthma model, the SHAP-HA complex has an inhibitory role in the development of airway hyperresponsiveness and allergic airway inflammation which may be attributed, at least in part, to negative feedback mechanisms exerted by sTNFR1, the shedding of which from the cell surface might also be promoted by the SHAP-HA complex.

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“…findings correlate well with the asthma model reported by Zosky et al [29] . Sera from KO mice showed a similar level of IgE and a higher level of IgG1 compared to WT mice.…”

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Deficiency in the Serum-Derived Hyaluronan-Associated Protein-Hyaluronan Complex Enhances Airway Hyperresponsiveness in a Murine Model of Asthma

Zhu

Zhuo

Kimata

et al. 2010

Int Arch Allergy Immunol

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“…The dependence of most of the components of this response, including AHR, on STAT6 signaling is not surprising, considering the strong connection between STAT6 and AHR and the Th2-associated airway inflammation that has been found in multiple studies of allergic asthma (32)(33)(34). The association of the inflammatory response we describe here in BALB/c mice with STAT6 is more complex than a simple Th2 differentiation decision.…”

Section: Discussionmentioning

confidence: 74%

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Swain

Meissner²,

Siemsen³

et al. 2012

Am J Respir Cell Mol Biol

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It is widely held that exposure to pathogens such as fungi can be an agent of comorbidity, such as exacerbation of asthma or chronic obstructive pulmonary disease. Although many studies have examined allergic responses to fungi and their effects on pulmonary function, the possible pathologic implications of the early innate responses to fungal pathogens have not been explored. We examined early responses to the atypical fungus Pneumocystis in two common strains of mice in terms of overall immunological response and related pathology, such as cell damage and airway hyperresponsiveness (AHR). We found a strong strain-specific response in BALB/c mice that included recruitment of neutrophils, NK, NKT, and CD4 T cells. This response was accompanied by elevated indicators of lung damage (bronchoalveolar lavage fluid albumin and LDH) and profound AHR. This early response was absent in C57BL/6 mice, although both strains exhibited a later response associated with the clearance of Pneumocystis. We found that this AHR could not be attributed exclusively to the presence of recruited neutrophils, NKT, NK, or CD4 cells or to the actions of IFN-g or IL-4. However, in the absence of STAT6 signaling, AHR and inflammatory cell recruitment were virtually absent. Gene expression analysis indicated that this early response included activation of several transcription factors that could be involved in pulmonary remodeling. These results show that exposure to a fungus such as Pneumocystis can elicit pulmonary responses that may contribute to morbidity, even without prior sensitization, in the context of certain genetic backgrounds.Keywords: STAT6; airway hyperresponsiveness; Pneumocystis; pulmonary inflammation; strain-specificThe immunological response to respiratory pathogens is normally calibrated to eliminate an infection without causing overt collateral damage to the respiratory tissue. In spite of this, an overexuberant or misdirected immune response can have pathological outcomes. This can range from phenomena that are transient and typically moderate, such as elevated airway hyperresponsiveness (AHR), to those that are permanent and progressive, such as pulmonary fibrosis. The health effects of these immunological responses depend on the context of the infection; those that are comorbid with other acute or chronic pulmonary conditions may incite serious respiratory distress in that context when otherwise they might have little noticeable effect.One area in which the effects of comorbid respiratory illnesses are especially relevant is that of exacerbation of preexisting asthma or chronic obstructive pulmonary disease (COPD). Many potential pathogens have been implicated as causing exacerbation; the most well known are various viruses, including rhinovirus, metapneumovirus, and respiratory syncytial virus (1). Several respiratory bacteria, most notably the atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae, have also been implicated in the exacerbation of asthma symptoms (2). Common fungi have also been widely imp...

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“…First, species differences may be responsible; BBS might increase the risk for asthma in humans but not in mice. Although the ovalbumin sensitization model is widely used in asthma research, it is not identical to human asthma (40). Second, perhaps loss of BBS does predispose to ''asthma'' in mice, but the tests we used were not sufficiently sensitive to detect it.…”

Section: Discussionmentioning

confidence: 99%

Loss of Bardet–Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia

Shah

Farmen²,

Moninger³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

107

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Mutations in a group of genes that contribute to ciliary function cause Bardet-Biedl syndrome (BBS). Most studies of BBS have focused on primary, sensory cilia. Here, we asked whether loss of BBS proteins would also affect motile cilia lining the respiratory tract. We found that BBS genes were expressed in human airway epithelia, and BBS2 and BBS4 localized to cellular structures associated with motile cilia. Although BBS proteins were not required for ciliogenesis, their loss caused structural defects in a fraction of cilia covering mouse airway epithelia. The most common abnormality was bulges filled with vesicles near the tips of cilia. We discovered this same misshapen appearance in airway cilia from Bbs1, Bbs2, Bbs4, and Bbs6 mutant mice. The structural abnormalities were accompanied by functional defects; ciliary beat frequency was reduced in Bbs mutant mice. Previous reports suggested BBS might increase the incidence of asthma. However, compared with wild-type controls, neither airway hyperresponsiveness nor inflammation increased in Bbs2 Ϫ/Ϫ or Bbs4 ؊/؊ mice immunized with ovalbumin. Instead, these animals were partially protected from airway hyperresponsiveness. These results emphasize the role of BBS proteins in both the structure and function of motile cilia. They also invite additional scrutiny of motile cilia dysfunction in patients with this disease.asthma ͉ basal body

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Ovalbumin‐sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation

Abstract: The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.

Cited by 65 publications

References 43 publications

Deficiency in the Serum-Derived Hyaluronan-Associated Protein-Hyaluronan Complex Enhances Airway Hyperresponsiveness in a Murine Model of Asthma

Deficiency in the Serum-Derived Hyaluronan-Associated Protein-Hyaluronan Complex Enhances Airway Hyperresponsiveness in a Murine Model of Asthma

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Loss of Bardet–Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia

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