Chronic aeroallergen during infancy enhances eotaxin-3 expression in airway epithelium and nerves.
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.
Chou
Debbie L
DL
Center for Comparative Respiratory Biology and Medicine, University of California Davis, 95616, USA.
Daugherty
Bruce L
BL
McKenna
Erin K
EK
Hsu
Willy M
WM
Tyler
Nancy K
NK
Plopper
Charles G
CG
Hyde
Dallas M
DM
Schelegle
Edward S
ES
Gershwin
Laurel J
LJ
Miller
Lisa A
LA
D000397:Air Pollution; D000485:Allergens / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis*; D017931:DNA Primers / Q000737:chemistry; D003713:Dendritic Cells / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D006969:Hypersensitivity, Immediate / Q000276:immunology; D008168:Lung / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008856:Microscopy, Fluorescence; D008925:Mites / Q000276:immunology / Q000378:metabolism; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000485:Allergens; C515456:CCL11 protein, human; C515484:CCL24 protein, human; C120429:CCL26 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D017931:DNA Primers; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D012313:RNA