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The mechanisms regulating the selective migration and degranulation of eosinophils in the asthmatic lung and the subsequent development of airways hyperreactivity (AHR) have not been fully delineated. In this investigation, we have employed a novel transgene model to facilitate the dissection of the contributions of IL-5 and/or eotaxin to eosinophil function in the absence of complex tissue signals derived from the allergic lung. Gene transfer of IL-5 and/or eotaxin to the lungs of naive mice induced a pronounced and selective airways eosinophilia, but did not result in eosinophil degranulation or AHR. Airways eosinophilia occurred independently of the induction of a blood eosinophilia, but was markedly augmented by the coexpression of both cytokines and/or by the transient mobilization of eosinophils from the bone marrow by the administration of i.v. IL-5. However, for eosinophil degranulation and AHR to occur, the inhalation of Ag was required in association with IL-5 and eotaxin expression. Investigations in IL-5-deficient mice linked eosinophilia, and not solely IL-5 and eotaxin, with the induction of AHR. Furthermore, eosinophil degranulation and AHR were dependent on CD4+ T cells. Importantly, this investigation shows that IL-5 regulates eosinophilia within the lung as well as in the circulation and also amplifies eotaxin-induced chemotaxis in the airway compartment. Moreover, the interplay between these cytokines, CD4+ T cells, and factors generated by Ag inhalation provides fundamental signals for eosinophil degranulation and the induction of AHR.

Type

Journal article

Journal

J Immunol

Publication Date

15/02/2000

Volume

164

Pages

2142 - 2150

Keywords

Administration, Intranasal, Animals, Bronchial Hyperreactivity, CD4-Positive T-Lymphocytes, Cell Degranulation, Chemokine CCL11, Chemokines, CC, Chemotactic Factors, Eosinophil, Chemotaxis, Leukocyte, Choline, Cytokines, Eosinophilia, Eosinophils, Genetic Vectors, Injections, Intravenous, Interleukin-5, Lung, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, Vaccinia virus