Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/27238

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Title
Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by INF-γ (Mig, CXCL9)
Author/Creator
Fulkerson, Patricia C.;  Zimmermann, Nives;  Yang, Ming;  Foster, Paul S.;  Rothenberg, Marc E.;  Brandt, Eric B.;  Muntel, Emily E.;  Doepker, Matthew P.;  Kavanaugh, Jessica L.;  Mishra, Anil;  Witte, David P.;  Zhang, Hongwei;  Farber, Joshua M.
Description
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 IFN-γ (Mig), and IFN-γ-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 (≈10–30 µg/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.
Relation
Proceedings of the National Academy of Sciences of the USA Vol. 101, Issue 7, p. 1987-1992
Publisher Link
http://dx.doi.org/10.1073/pnas.0308544100
Date
2004
Publisher
National Academy of Sciences
Keyword(s)
allergy;  asthma;  cytokine;  eotaxin
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/27238
Identifier
ISSN:0027-8424
Reviewed
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Subject
"Proceedings of the National Academy of Sciences of the USA"
 
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