Fizz1/Relm-945; Mediates IL-13r945;1-independent Eosinophil Recruitment

A. Munitz, R. Korman, M. Mingler, M.E. Rothenberg

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Fizz1/Relm-945; Mediates IL-13r945;1-independent Eosinophil Recruitment


RATIONALE: FIZZ1/Relm-945;, is a secreted protein and hallmark signature gene of murine alternatively activated macrophages. FIZZ1/Relm-945; is highly induced by allergic inflammatory triggers (e.g. IL-13, IL-4) yet its function remains unclear. Previously we have shown that eosinophil recruitment in a two-antigen challenge OVA model of experimental-asthma is mainly IL-13R945;1 independent. However, the mechanistic basis for this observation is unknown. METHODS: FIZZ1/Relm-945; expression (pPCR, ELISA), BALF (differential cell counts) and histology (H&E, PAS) were analyzed following induction of experimental asthma (i.e. OVA and the relatively chronic Aspergillus-fumigatus models) in wild-type and Il13ra1-/- mice. The cellular source for Relm-945; expression was analyzed following intratracheal IL-13 delivery and experimental-asthma induction (immunoflourescence). FIZZ1/Relm-945; (2-20 956;g) was intraperitonelly injected into wild-type mice and peritoneal lavage performed following 24-48 hrs. Eosinophils were purified from CD2-IL-5-transgenic mice and chemotaxis towards FIZZ1/Relm-945; examined (transwells). RESULTS: Following experimental-asthma induction, Relm-945; mRNA and protein expression were significantly induced (BALF, 9-12 ng/ml compared with 2-3 ng/ml in control mice). Interestingly, Relm-945; induction was IL-13R945;1-independent in the OVA model, but entirely IL-13945;1-dependent in the chronic Asp model. Relm-945; directly correlated with inflammatory cell (mainly eosinophil) infiltration that was IL-13R945;1-independent and -dependent in the OVA and Asp models, respectively. Following IL-13 administration, Relm-945; was highly over-expressed by epithelial cells, macrophages and eosinophils while OVA-induced Relm-945; was expressed only in epithelial cells and macrophages. Intraperitoneal Relm-945; administration induced peritoneal eosinophilia and Relm-945; induced eosinophil chemotaxis in-vitro. CONCLUSIONS: These results define a new role for Relm-945; as an alternative pathway for eosinophil recruitment independent of IL-13R945;1.

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American Academy of Allergy Asthma & Immunology