- Title
- Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by INF-γ (Mig, CXCL9)
- 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.
- 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
- Publisher
- National Academy of Sciences
- Resource Type
- journal article
- Date
- 2004
- 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.
- Subject
- allergy; asthma; cytokine; eotaxin
- Identifier
- uon:1493
- Identifier
- http://hdl.handle.net/1959.13/27238
- Identifier
- ISSN:0027-8424
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