期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 7, 页码 1987-1992出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0308544100
关键词
allergy; asthma; cytokine; eotaxin
资金
- NIAID NIH HHS [R01 AI42242, AI45898, R37 AI045898, R01 AI045898] Funding Source: Medline
- NIAMS NIH HHS [R01 AR042242] Funding Source: Medline
Experimental analysis of allergic airway inflammation (AAI) in animals and humans is associated with coordinate gene induction. Using DNA microarray analysis, we have identified a large panel of AAI signature genes. Unexpectedly, the allergen-challenged lung (a T helper 2 microenvironment) was found to be associated with the expression of T helper 1-associated CXCR3 ligands, monokine induced by lFN-gamma(Mig),and IFN-gamma-inducible protein of 10 kDa(IP-10). Here we report that Mig functions as a negative regulator of murine eosinophils. Whereas Mig was not able to induce chemotaxis of eosinophils, pretreatment with Mig induced a dose-dependent inhibition of chemoattractant-induced eosinophil transmigration in vitro. Moreover, i.v. administration of low doses of Mig (approximate to10-30 mug/kg) induced strong and specific dose-dependent inhibition of chemokine-, IL-13-, and allergen-induced eosinophil recruitment and, conversely, neutralization of Mig before allergen challenge increased airway eosinophilia. Importantly, Mig also inhibited a CCR3-mediated functional response in eosinophils. These results indicate that the ultimate distribution and function of inflammatory cells within the allergic lung is dictated by a balance between positively and negatively regulatory chemokines. The identification of a naturally occurring eosinophil inhibitory chemokine pathway in vivo provides a strategic basis for future therapeutic consideration.
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