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Departments of
*
Pathology and
Internal Medicine, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI 48109; and
National Institute of Aging, National Institutes of Health, Baltimore, MD 21224
The immunomodulatory role of the chemokine C10 was explored in
allergic airway responses during experimental allergic bronchopulmonary
aspergillosis (ABPA). The intratracheal delivery of Asperigillus
fumigatus Ag into A. fumigatus-sensitized mice
resulted in significantly increased levels of C10 within the
bronchoalveolar lavage, and these levels peaked at 48 h after
A. fumigatus challenge. In addition, C10 levels in BAL
samples were greater than 5-fold higher than levels of other chemokines
such as monocyte-chemoattractant protein-1, eotaxin, and
macrophage-inflammatory protein-1
. From in vitro studies, it was
evident that major pulmonary sources of C10 may have included alveolar
macrophages, lung fibroblasts, and vascular smooth muscle cells.
Experimental ABPA was associated with severe peribronchial
eosinophilia, bronchial hyperresponsiveness, and augmented IL-13 and
IgE levels. The immunoneutralization of C10 with polyclonal
anti-C10 antiserum 2 h before the intratracheal A.
fumigatus challenge significantly reduced the airway
inflammation and hyperresponsiveness in this model of ABPA, but had no
effect on IL-10 nor IgE levels. Taken together, these data suggest that
C10 has a unique role in the progression of experimental
ABPA.
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