Interleukin-6 and the granulocyte colony-stimulating factor receptor are major independent regulators of granulopoiesis in vivo but are not required for lineage commitment or terminal differentiation.
Multiple hematopoietic cytokines can stimulate granulopoiesis; however, their relative importance in vivo and mechanisms of action remain unclear. We recently reported that granulocyte colony-stimulating factor receptor (G-CSFR)-deficient mice have a severe quantitative defect in granulopoiesis despite which phenotypically normal neutrophils were still detected. These results confirmed a role for the G-CSFR as a major regulator of granulopoiesis in vivo, but also indicated that G-CSFR independent mechanisms of granulopoiesis must exist. To explore the role of interleukin-6 (IL-6) in granulopoiesis, we generated IL-6 x G-CSFR doubly deficient mice. The additional loss of IL-6 significantly worsened the neutropenia present in young adult G-CSFR-deficient mice; moreover, exogenous IL-6 stimulated granulopoiesis in vivo in the absence of G-CSFR signals. Near normal numbers of myeloid progenitors were detected in the bone marrow of IL-6 x G-CSFR-deficient mice and their ability to terminally differentiate into mature neutrophils was observed. These results indicate that IL-6 is an independent regulator of granulopoiesis in vivo and show that neither G-CSFR or IL-6 signals are required for the commitment of multipotential progenitors to the myeloid lineage or for their terminal differentiation.
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Department of Medicine, Washington University Medical School, St Louis, MO 63110-1093, USA.
Poursine-Laurent
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D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D015850:Interleukin-6 / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009503:Neutropenia / Q000235:genetics / Q000503:physiopathology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019947:Receptors, Interleukin-6 / Q000502:physiology*
D015850:Interleukin-6; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D019947:Receptors, Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor