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Am J Physiol Lung Cell Mol Physiol 282: L1066-L1074, 2002. First published December 21, 2001; doi:10.1152/ajplung.00195.2001
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Vol. 282, Issue 5, L1066-L1074, May 2002

CD4+ T cell-dependent airway mucus production occurs in response to IL-5 expression in lung

J. Paul Justice1, J. Crosby1, M. T. Borchers2, A. Tomkinson3, J. J. Lee2, and N. A. Lee1

1 Divisions of Hematology/Oncology and 2 Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259; and 3 Pharmaceutical Division, Department of Biotechnology, Bayer Corporation, Berkeley, California 94701-1986

The potential role of airway interleukin-5 (IL-5) expression in eliciting mucus production was demonstrated in a pulmonary IL-5 transgenic mouse model (NJ.1726) in which naive transgenic mice display comparable levels of airway mucus relative to allergen-sensitized and -challenged wild-type mice. The intrinsic mucus accumulation of NJ.1726 was abolished in compound transgenic-gene knockout mice deficient of either CD4+ cells [NJ.1726/CD4(-/-)] or alpha beta T cell receptor-positive (TCR+) cells [NJ.1726/alpha beta TCR(-/-)]. In addition, mucus production in naive NJ.1726 was inhibited by >90% after administration of the soluble anti-IL-4 receptor alpha -subunit antagonist. The loss of mucus production in NJ.1726/CD4(-/-), NJ.1726/alpha beta TCR(-/-), and anti-IL-4 receptor alpha -subunit antagonist-treated mice occurred notwithstanding the significant pulmonary eosinophilia and expansion of airway B cells induced by ectopic IL-5 expression. Furthermore, the loss of mucus accumulation occurred in these mice despite elevated levels of airway and peripheral IL-5, indicating that IL-5 does not directly induce goblet cell metaplasia and mucus production. Thus pulmonary expression of IL-5 alone is capable of inducing CD4+ T cell-dependent goblet cell metaplasia, apparently mediated by IL-4 receptor alpha -subunit-ligand interactions, and represents a previously unrecognized novel pathway for augmenting allergen-induced mucus production.

asthma; goblet cell; transgenic; gene knockout


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