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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3349-3354.
Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-10-3438.
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HEMATOPOIESIS
Interleukin-6 deficiency affects bone marrow stromal precursors, resulting in defective hematopoietic support
María del Carmen Rodríguez,
Antonio Bernad, and
Miguel Aracil
From the Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus de Cantoblanco, Madrid, Spain.
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. (Blood. 2004;103:3349-3354)
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