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Perspectives in inflammation biology pp 91–110Cite as

Role of Integrins α4 and β2 Onset and Development of Chronic Allergic Asthma in Mice

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Abstract

Objective. Chronic asthma is characterized by an ongoing recruitment of inflammatory cells and airway hyperresponsiveness leading to structural airway remodeling. Although α4b1 and β2 integrins regulate leukocyte migration in inflammatory diseases and play decisive roles in acute asthma, their role has not been explored under the chronic asthma setting. To extend our earlier studies with α4Δ/Δ and β2L/L mice, which showed that both α4 and β2 integrins have nonredundant regulatory roles in acute ovalbumin (OVA)-induced asthma, we explored to what extent these molecular pathways control development of structural airway remodeling in chronic asthma.

Materials and Methods. Control, α4Δ/Δ, and β2L/L mouse groups, sensitized by intraperitoneal OVA as allergen, received intratracheal OVA periodically over days 8–55 to induce a chronic asthma phenotype. Post-OVA assessment of inflammation and pulmonary function (airway hyperresponsiveness), together with airway modeling measured by goblet cell metaplasia, collagen content of lung, and transforming growth factor b1 expression in lung homogenates were evaluated.

Results. In contrast to control and β2L/L mice, α4Δ/Δ mice failed to develop and maintain the composite chronic asthma phenotype evaluated as mentioned, and subepithelial collagen content was comparable to baseline. These data indicate that β2 integrins, although required for inflammatory migration in acute asthma, are dispensable for structural remodeling in chronic asthma.

Conclusion. α4 integrins appear to have a regulatory role in directing transforming growth factor b-induced collagen deposition and structural alterations in lung architecture likely through interactions of Th2 cells, eosinophils, or mast cells with endothelium, resident airway cells, and/or extracellular matrix.

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  1. Banerjee ER, Jiang Y, Henderson Jr WR, Latchman YL, Papayannopoulou T. Absence of α4 but not β2 integrins restrains the development of chronic allergic asthma using mouse genetic models. Exp Hematol. 2009;37:715–27.

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  1. Immunology & Regenerative Medicine Research Unit, University College of Science, Technology and Agriculture, Kolkata, India

    Ena Ray Banerjee

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Banerjee, E.R. (2014). Role of Integrins α4 and β2 Onset and Development of Chronic Allergic Asthma in Mice. In: Perspectives in inflammation biology. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1578-3_4

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