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 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.
Peled
A
A
The Center for Blood Research, Inc, Boston, MA, USA.
Gonzalo
J A
JA
Lloyd
C
C
Gutierrez-Ramos
J C
JC
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D019742:Chemokines, CC; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D004357:Drug Synergism; D004802:Eosinophilia / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D037342:Pertussis Toxin; D011014:Pneumonia / Q000473:pathology / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D019089:Stem Cell Factor / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D019742:Chemokines, CC; D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin; D037342:Pertussis Toxin