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Publication : Interleukin-6 deficiency affects bone marrow stromal precursors, resulting in defective hematopoietic support.

First Author  Rodríguez Mdel C Year  2004
Journal  Blood Volume  103
Issue  9 Pages  3349-54
PubMed ID  14701687 Mgi Jnum  J:90289
Mgi Id  MGI:3042821 Doi  10.1182/blood-2003-10-3438
Citation  Rodriguez Mdel C, et al. (2004) Interleukin-6 deficiency affects bone marrow stromal precursors, resulting in defective hematopoietic support. Blood 103(9):3349-54
abstractText  Interleukin-6 (IL-6) is a critical factor in the regulation of stromal function and hematopoiesis. In vivo bromodeoxyuridine incorporation analysis indicates that the percentage of Lin(-)Sca-1(+) hematopoietic progenitors undergoing DNA synthesis is diminished in IL-6-deficient (IL-6(-/-)) bone marrow (BM) compared with wild-type BM. Reduced proliferation of IL-6(-/-) BM progenitors is also observed in IL-6(-/-) long-term BM cultures, which show defective hematopoietic support as measured by production of total cells, granulocyte macrophage-colony-forming units (CFU-GMs), and erythroid burst-forming units (BFU-Es). Seeding experiments of wild-type and IL-6(-/-) BM cells on irradiated wild-type or IL-6-deficient stroma indicate that the hematopoietic defect can be attributed to the stromal and not to the hematopoietic component. In IL-6(-/-) BM, stromal mesenchymal precursors, fibroblast CFUs (CFU-Fs), and stroma-initiating cells (SICs) are reduced to almost 50% of the wild-type BM value. Moreover, IL-6(-/-) stromata show increased CD34 and CD49e expression and reduced expression of the membrane antigens vascular cell adhesion molecule-1 (VCAM-1), Sca-1, CD49f, and Thy1. These data strongly suggest that IL-6 is an in vivo growth factor for mesenchymal precursors, which are in part implicated in the reduced longevity of the long-term repopulating stem cell compartment of IL-6(-/-) mice.
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