THE CHEMOTACTIC CYTOKINE EOTAXIN ACTS AS A GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR DURING LUNG INFLAMMATION

During inflammatory processes, inflamed tissues signal the bone marrow (BM) to produce more mature leukocytes in ways that are not yet under stood. We report here that, during the development of lung allergic in flammation, the administration of neutralizing antibodies to the chemo tactic cytokine, Eotaxin, prevented the increase in the number of myel oid progenitors produced in the BM, therefore reducing the output of m ature myeloid cells from BM. Conversely, the in vivo administration of Eotaxin increased the number of myeloid progenitors present in the BM . Furthermore, we found that, in vitro, Eotaxin is a colony-stimulatin g factor for granulocytes and macrophages. Eotaxin activity synergized with stem cell factor but not with interleukin-3 or granulocyte-macro phage colony-stimulating factor and was inhibited by pertussis toxin. We report also that CCR-3, the receptor for Eotaxin, was expressed by hematopoietic progenitors (HP). Thus, during inflammation, Eotaxin act s in a paracrine way to shift the differentiation of BM HP towards the myeloid lineage. (C) 1998 by The American Society of Hematology.