Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages

Eosinophils are associated with allergic diseases and helminth infections. Development of these cells and recruitment to peripheral tissues are only partially understood. Distinct stages of eosinophil development in fetal liver, bone marrow, and blood could be identified using IL-4 reporter mice and mAb against FIRE, Siglec-F, and CCR3. Immature eosinophils were present in the fetal liver and could reconstitute the eosinophil compartment in irradiated recipient mice. In adult mice, eosinophil maturation proceeded from CCR3(-) to CCR3(+) cells in the bone marrow and was accompanied with changes in the transcriptional profile. Eosinophils appeared as activated cells in lung, thymus, lymph nodes, and Peyer's patches but remained in a resting state in bone marrow, blood, and spleen. Mixed bone marrow chimeras revealed that recruitment to lung and peritoneum was dependent on Stat6 expression in noneosinophils. Alternatively activated macrophages contributed substantially to tissue recruitment of eosinophils, providing a novel basis for development of therapeutic approaches to lower tissue eosinophilia.