Characterization of a Murine Model of Allergic Pulmonary Inflammation

Kung, Ted T.; Jones, Howard; Adams, G. K.; Umland, Shelby P.; Kreutner, William; Egan, Robert W.; Chapman, R W; Watnick, Arthur S.

doi:10.1159/000236807

Cited by 211 publications

(178 citation statements)

References 12 publications

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“…Since allergic asthma has many hallmarks of a T H 2-type response in humans and in animal models, we tested whether ITK may be involved in the allergic inflammatory response in the lung to the model allergen OVA in a murine model of allergic asthma. In this model, mice are primed with OVA, then challenged IN with OVA (42). This treatment results in increased inflammatory cell infiltration into the lung, thickening of the epithelial cells lining the bronchioles of the lung, mucous secretion, and increases in IgE in the serum of these mice.…”

Section: Itk Null Mice Exhibit Reduced Lung Inflammation Following Almentioning

confidence: 99%

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Mueller

August

2003

The Journal of Immunology

147

137

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Allergic asthma patients manifest airway inflammation and some show increases in eosinophils, TH2 cells, and cytokines, increased mucous production in the lung, and elevated serum IgE. This TH2-type response suggests a prominent role for TH2 cells and their cytokines in the pathology of this disease. The Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) has been shown to play a role in the differentiation and/or function of TH2-type cells, suggesting that ITK may represent a good target for the control of asthma. Using a murine model of allergic asthma, we show here that ITK is involved in the development of immunological symptoms seen in this model. We show that mice lacking ITK have drastically reduced lung inflammation, eosinophil infiltration, and mucous production following induction of allergic asthma. Notably, T cell influx into the lung was reduced in mice lacking ITK. T cells from ITK−/− mice also exhibited reduced proliferation and cytokine secretion, in particular IL-5 and IL-13, in response to challenge with the allergen OVA, despite elevated levels of total IgE and increased OVA-specific IgE responses. Our results suggest that the tyrosine kinase ITK preferentially regulates the secretion of the TH2 cytokines IL-5 and IL-13 and may be an attractive target for antiasthmatic drugs.

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Section: Itk Null Mice Exhibit Reduced Lung Inflammation Following Almentioning

confidence: 99%

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Mueller

August

2003

The Journal of Immunology

147

137

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“…On days 14, 24, 25, and 26, mice were challenged intranasally with 100 g of OVA in 0.1 ml of normal saline. In protocol B, mice were immunized on days 0 and 5 with 8 g of OVA in alum (1:1 in alum in 0.1 ml), as described earlier (23). On day 12, mice received 100 g of OVA in 0.1 ml of normal saline.…”

Section: Mouse Models Of Airway Allergic Inflammationmentioning

confidence: 99%

“…Therefore, we examined whether the requirement for CCR8 to affect the outcome of airway inflammation was masked by the dosage and timing of Ag challenge. In protocol B, mice were immunized with lower doses of Ag, as described previously (23). CCR8 Ϫ/Ϫ mice and WT littermates were sensitized on days 0 and 5 with 8 g of OVA, and later challenged with a single intranasal dose of OVA on day 12.…”

Section: Effect Of Ag Dose On Allergic Airway Inflammation In Ccr8 ϫ/mentioning

confidence: 99%

CCR8 Is Not Essential for the Development of Inflammation in a Mouse Model of Allergic Airway Disease

Chung¹,

Kuo²,

Kumer³

et al. 2003

The Journal of Immunology

104

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Chemokine receptors play an important role in the trafficking of various immune cell types to sites of inflammation. Several chemokine receptors are differentially expressed in Th1 and Th2 effector populations. Th2 cells selectively express CCR3, CCR4, and CCR8, which could direct their trafficking to sites of allergic inflammation. Additionally, increased expression of the CCR8 ligand, TCA-3, has been detected in affected lungs in a mouse model of asthma. In this study, CCR8-deficient mice were generated to address the biological role of CCR8 in a model of allergic airway disease. Using two different protocols of allergen challenge, we demonstrate that absence of CCR8 does not affect the development of pulmonary eosinophilia and Th2 cytokine responses. In addition, administration of anti-TCA-3-neutralizing Ab during allergen sensitization and rechallenge failed to inhibit airway allergic inflammation. These results suggest that CCR8 does not play an essential role in the pathogenesis of inflammation in this mouse model of allergic airway disease.

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“…[5][6][7][8][9][10] However, these responses have typically been assessed in isolation from each other. We have recently demonstrated that C57BL/6J mice undergo a biphasic response to aerosolized ovalbumin (OVA) exposure.…”

mentioning

confidence: 99%

Chronic Inhaled Ovalbumin Exposure Induces Antigen-Dependent but Not Antigen-Specific Inhalational Tolerance in a Murine Model of Allergic Airway Disease

Schramm

Puddington

et al. 2004

The American Journal of Pathology

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Sensitized mice acutely challenged with inhaled ovalbumin (OVA) develop allergic airway inflammation, characterized by OVA-specific IgE production, airway eosinophilia, increased pulmonary B and T lymphocytes, and airway hyperreactivity. In this study, a chronic exposure model was developed and two distinct patterns of response were observed. Discontinuous inhalational exposure to OVA (6 weeks) produced airway inflammation and hyperreactivity that were similar to acute (10 days) responses. Continuous inhalational exposure to OVA (6 or 11 weeks) resulted in attenuation of airway eosinophilia and hyperresponsiveness without reduction of OVA-specific IgE and IgG 1 levels. The inhibition of airway inflammation was dependent on continuous exposure to antigen, because continuously exposed mice with attenuated inflammatory responses redeveloped allergic airway disease if the OVA aerosols were interrupted and then restarted (11-week-discontinuous). Inhalational tolerance induced by continuous OVA exposure demonstrated bystander suppression of cockroach allergen-mediated airway eosinophilia. These findings may be attributed to changes in production of the anti-inflammatory cytokine interleukin-10 during continuous OVA aerosol exposure. The symptomatic and asymptomatic allergic responses in human asthmatics could be explained by similar variable or discontinuous exposures to aeroantigens. Throughout the past 40 years, the prevalence of allergic disease, including atopic dermatitis, hay fever, and asthma, has risen dramatically in the developed world. This disturbing trend is documented best for asthma. 1,2 A wealth of clinical and experimental data suggests that allergic asthma is due to an aberrant lung immune response mediated through T-helper type 2 cells (Th2 cells) and associated cytokine-signaling pathways. The normal lung is able to distinguish between airborne antigens associated with infectious agents, to which an immunological response is generated, and harmless inhaled antigens, which are usually ignored. In the asthmatic lung, some of these normally harmless antigens activate specific Th2 cells and elicit an inflammatory response characterized by Th2 cytokine production, eosinophilic airway inflammation, airway hyperresponsiveness, and bronchoconstriction. These pulmonary responses may be accompanied by systemic allergic sensitization, manifested by elevated titers of antigen-specific IgE. The mechanisms that control CD4 ϩ T lymphocyte polarization to allergenic Th2 phenotypes are incompletely understood but seem to involve genetic predispositions, local factors such as pre-existing cytokine concentrations and inflammation, and antigenic factors (ie, potency, dose, and duration of exposure).Several investigators have used mouse models to investigate the mechanisms of inhalational tolerance to antigens 3,4 or of allergic airway sensitization. [5][6][7][8][9][10] However, these responses have typically been assessed in isolation from each other. We have recently demonstrated that C57BL/6J mice undergo a biphasic...

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Characterization of a Murine Model of Allergic Pulmonary Inflammation

Cited by 211 publications

References 12 publications

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

CCR8 Is Not Essential for the Development of Inflammation in a Mouse Model of Allergic Airway Disease

Chronic Inhaled Ovalbumin Exposure Induces Antigen-Dependent but Not Antigen-Specific Inhalational Tolerance in a Murine Model of Allergic Airway Disease

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