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1 Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229; and 2 Department of Environmental Medicine, University of Rochester, Rochester, New York 14642
Clara cell secretory protein (CCSP) is an
abundant 10-kDa polypeptide synthesized and secreted primarily by
nonciliated bronchiolar epithelial cells in the mammalian lung. To
determine the potential role of CCSP in pulmonary inflammation after
acute viral infection, CCSP gene-targeted {CCSP-deficient
[CCSP(
/)]} mice were exposed to a
recombinant E1- and E3-deficient adenoviral vector, Av1Luc1, intratracheally. Lung inflammation was markedly increased in
CCSP(/) mice compared with wild-type control mice and was
associated with an increased number of polymorphonuclear cell
infiltrates and epithelial cell injury in both conducting airways and
alveolar regions. Histological evidence of pulmonary inflammation in
CCSP(/) mice was associated with increased production of
cytokine (interleukin-1
and -6 and tumor necrosis factor-
) mRNA
and protein, as well as chemokine (macrophage inflammatory protein-1
and -2 and monocyte chemoattractant protein-1) mRNA expression within
the lung in response to adenoviral infection. Adenoviral-mediated gene
transfer was decreased in CCSP(/) mice relative to
wild-type mice as measured by luciferase enzyme activity in lung
homogenates. The present study suggests that CCSP is involved in
modulating lung inflammation during viral infection and supports a role
for CCSP in lung host defense.
lung epithelium; pulmonary infection; viral pathogenesis
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