SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis
- Author(s)
- Croker, BA; Metcalf, D; Robb, L; Wei, W; Mifsud, S; DiRago, L; Cluse, LA; Sutherland, KD; Hartley, L; Williams, E; Zhang, JG; Hilton, DJ; Nicola, NA; Alexander, WS; Roberts, AW;
- Details
- Publication Year 2004-02,Volume 20,Issue #2,Page 153-165
- Journal Title
- IMMUNITY
- Publication Type
- Journal Article
- Abstract
- To determine the importance of suppressor of cytokine signaling-3 (SOCS3) in the regulation of hematopoietic growth factor signaling generally, and of G-CSFinduced cellular responses specifically, we created mice in which the Socs3 gene was deleted in all hematopoietic cells. Although normal until young adulthood, these mice then developed neutrophilia and a spectrum of inflammatory pathologies. When stimulated with G-CSF in vitro, SOCS3-deficient cells of the neutrophilic granulocyte lineage exhibited prolonged STAT3 activation and enhanced cellular responses to G-CSF, including an increase in cloning frequency, survival, and proliferative capacity. Consistent with the in vitro findings, mutant mice injected with G-CSF displayed enhanced neutrophilia, progenitor cell mobilization, and splenomegaly, but unexpectedly also developed inflammatory neutrophil infiltration into multiple tissues and consequent hind-leg paresis. We conclude that SOCS3 is a key negative regulator of G-CSF signaling in myeloid cells and that this is of particular significance during G-CSF-driven emergency granulopoiesis.
- Publisher
- CELL PRESS
- Keywords
- COLONY-STIMULATING FACTOR; BLOOD PROGENITOR CELLS; CYTOKINE SIGNALING-3; PERIPHERAL-BLOOD; FACTOR-RECEPTOR; IN-VIVO; HUMAN-NEUTROPHILS; REPORTER STRAIN; TRANSGENIC MICE; BONE-MARROW
- Publisher's Version
- https://doi.org/10.1016/S1074-7613(04)00022-6
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- Refer to copyright notice on published article.
Creation Date: 2004-02-01 12:00:00