Cytokine production and function in c-mpl-deficient mice: No physiologic role for interleukin-3 in residual megakaryocyte and platelet production
- Author(s)
- Gainsford, T; Roberts, AW; Kimura, S; Metcalf, D; Dranoff, G; Mulligan, RC; Begley, CG; Robb, L; Alexander, WS;
- Details
- Publication Year 1998-04-15,Volume 91,Issue #8,Page 2745-2752
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- Mice lacking thrombopoietin (TPO), or its receptor c-Mpl, display defective megakaryocyte and platelet development and deficiencies in progenitor cells of multiple hematopoietic lineages. The contribution of alternative cytokines to thrombopoiesis in the absence of TPO signalling was examined in mpl(-/-) mice. Analysis of serum and organ-conditioned media showed no evidence of a compensatory overproduction of megakaryocytopoietic cytokines. However, consistent with a potential role in vivo, when injected into mpl(-/-) mice, interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) retained the capacity to elevate megakaryocytes and their progenitors in hematopoietic tissues and increase circulating platelet numbers, However, double mutant mice bred to carry genetic defects both in c-Mpl and IL-3 or the alpha chain of the IL-3 receptor, displayed no greater deficiencies in megakaryocytes or platelets than mpl-deficient animals, suggesting absence of a physiologic role for IL-3 in the residual megakaryocytopoiesis and platelet production in these mice. (C) 1998 by The American Society of Hematology.
- Publisher
- W B SAUNDERS CO
- Keywords
- LEUKEMIA INHIBITORY FACTOR; HEMATOPOIETIC STEM-CELLS; IN-VITRO; THROMBOPOIETIN; GROWTH; LIGAND; THROMBOCYTOPENIA; PROGENITORS; STIMULATION; LACKING
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Creation Date: 1998-04-15 12:00:00