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The Chemotactic Cytokine Eotaxin Acts as a Granulocyte-Macrophage
Colony-Stimulating Factor During Lung Inflammation
Amnon Peled,
Jose Angel Gonzalo,
Clare Lloyd, and
Jose-Carlos Gutierrez-Ramos
From The Center for Blood Research, Inc, and The Department of
Genetics, Harvard Medical School, Boston, MA; and Millennium
Pharmaceuticals, Inc, Cambridge, MA.
During inflammatory processes, inflamed tissues signal the bone
marrow (BM) to produce more mature leukocytes in ways that are not yet
understood. We report here that, during the development of lung
allergic inflammation, the administration of neutralizing antibodies to
the chemotactic cytokine, Eotaxin, prevented the increase in the number
of myeloid progenitors produced in the BM, therefore reducing the
output of mature 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-stimulating factor for granulocytes and macrophages. Eotaxin
activity synergized with stem cell factor but not with interleukin-3 or
granulocyte-macrophage 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 acts in a paracrine way to shift the
differentiation of BM HP towards the myeloid lineage.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 1909-1916
© 1998 by The American Society of Hematology.
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