Published ahead of print on April 15, 2005, doi:10.1165/rcmb.2004-0236RC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 1, July 2005, 1-8 A more recent version of this article appeared on July 1, 2005
Submitted on July 23, 2004 Chronic Aeroallergen During Infancy Enhances Eotaxin-3 Expression in Airway Epithelium and NervesDebbie L Chou1,1 Center for Comparative Respiratory Biology and Medicine and the California National Primate Research Center, University of California, Davis, Davis, CA, USA, 2 Merck Research Laboratories, Rahway, NJ, USA * To whom correspondence should be addressed. E-mail: lmiller{at}ucdavis.edu.
We have documented that exposure of rhesus monkeys to house dust mite aeroallergen during postnatal development resulted in significant recruitment of eosinophils into the airway mucosa (Clin. Exp. Allergy 33:1686-1694, 2003). Because eosinophils were not uniformly distributed throughout the five conducting airway generations examined, we speculated that trafficking within anatomic microenvironments of the lung is mediated by differential chemokine expression. To address this question, we used quantitative real-time RT-PCR to evaluate the related eosinophilic chemokines, eotaxin (CCL11), eotaxin-2 (CCL24) and eotaxin-3 (CCL26) within isolated airways of infant monkey lung. Overall, chemokine mRNA expression levels in house dust mite-exposed airways were as follows: eotaxin-3 > eotaxin > eotaxin-2. Immunofluorescence staining for eotaxin-3 and CC chemokine receptor 3 (CCR3) showed positive cells within epithelium and peripherally located nerve fiber bundles of the airway wall. Epithelial volume of eotaxin-3 within the trachea correlated with epithelial volume of major basic protein. CCR3+ and MHC Class II+ dendritic cells, but not eosinophils or mast cells, co-localized within eotaxin-3+ nerve fiber bundles. We conclude that localized expression of eotaxin-3 plays an important role in the recruitment of diverse CCR3+ cell populations to different anatomic microenvironments within the infant airway in response to chronic allergen exposure.
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