Murine eotaxin-2: A constitutive eosinophil chemokine induced by allergen challenge and IL-4 overexpression

The generation of tissue eosinophilia is governed in Dart by chemokines; in itial investigation has identified three chemokines in the human genome wit h eosinophil selectivity, referred to as eotaxin-1, -2, and -3, Elucidation of the role of these chemokines is dependent in part upon analysis of muri ne homologues; however, only one murine homologue, eotaxin-1, has been iden tified. We now report the characterization of the murine eotaxin-2 cDNA, ge ne and protein. The eotaxin-2 cDNA contains an open reading frame that enco des for a 119-amino acid protein, The mature protein, which is predicted to contain 93 amino acids, is most homologous to human eotaxin-2 (59.1% ident ity), but is only 38.9 % identical with murine eotaxin-1, Northern blot ana lysis reveals three predominant mRNA species and highest constitutive expre ssion in the jejunum and spleen. Additionally, allergen challenge in the lu ng with Asperigillus fumigatus or OVA revealed marked induction of eotaxin- 2 mRNA, Furthermore, eotaxin-2 mRNA was strongly induced by both transgenic over-expression of IL-4 in the lung and administration of intranasal IL-4. Analysis of eotaxin-2 mRNA expression in mice transgenic for IL-4 but gene tically deficient in STAT-6 revealed that the IL-l-induced expression was S TAT-6 dependent. Recombinant eotaxin-2 protein induced dose-dependent chemo tactic responses on murine eosinophils at concentrations between 1-1000 ng/ ml, whereas no activity was displayed on murine macrophages or neutrophils, Functional analysis of recombinant protein variants revealed a critical ro le for the amino terminus. Thus, murine eotaxin-2 is a constitutively expre ssed eosinophil chemokine likely to be involved in homeostatic, allergen-in duced, and IL-4-associated immune responses.