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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 
T cell receptor-positive
(TCR+) cells [NJ.1726/
TCR(
/
)]. In addition,
mucus production in naive NJ.1726 was inhibited by >90% after
administration of the soluble anti-IL-4 receptor
-subunit
antagonist. The loss of mucus production in NJ.1726/CD4(
/
),
NJ.1726/
TCR(
/
), and anti-IL-4 receptor
-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
-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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