期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 113, 期 6, 页码 1109-1116出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2004.03.022
关键词
eotaxin-1; eotaxin-2; eosinophils; BrdU; CD34(+) progenitors; airway; allergy
Background: Eosinophils develop from CD34(+) bone marrow progenitors, and evidence increasingly suggests that these progenitors are recruited to the airways in atopic asthmatics after allergen challenge. Moreover, it has been shown that the number of CD34(+) progenitors in bronchial tissue correlates with asthma severity. To date, however, little is known about how these cells are recruited into the airways. Objective: Our aim was to evaluate the role of 2 chemokines, eotaxin-1 and/or eotaxin-2, in the recruitment of newly produced and CD34(+) eosinophils to the airways after allergen exposure. Methods: BALB/c mice sensitized and exposed to ovalbumin were pretreated intraperitoneally or intranasally with a neutralizing anti-eotaxin-1 and/or anti-eotaxin-2 antibody. A thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), was used to mark newly produced cells. Bronchoalveolar lavage (BAL), blood, and bone marrow were collected 24 hours after the final exposure. Results: Anti-eotaxin-1 and/or anti-eotaxin-2 given intranasally (ie, locally to airways) significantly decreased BAL eosinophils. This decrease was paralleled with a decrease in both BrdU(+) and CD34+ eosinophils. In contrast, systemically administered (ie, intraperitoneally) anti-eotaxin-1 and/or anti-eotaxin-2 resulted in a significant decrease in BAL eosinophils only when the combined treatment was of a sufficiently high dosage to produce measurable concentrations in the airways. Furthermore, neither of the treated groups showed any significant decrease in blood or bone marrow eosinophils. Conclusion: Both eotaxin-1 and eotaxin-2 are involved locally within the airways in the regulation of the recruitment of newly produced and CD34(+) eosinophils after allergen exposure.
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