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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-03-0735.
Submitted March 11, 2002
Accepted September 4, 2002
Constitutive overexpression of IL-5 induces extramedullary hematopoiesis in the spleen
Sophia Khaldoyanidi, Lyudmila Sikora, David H Broide, Marc E Rothenberg, and P Sriramarao*
Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA, USA
Department of Medicine, University of California San Diego, La Jolla, CA, USA
Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH, USA
* Corresponding author; email: rao{at}ljimm.org.
The differentiation of eosinophils from hematopoietic precursors and their subsequent maturation, chemotaxis and activation is primarily regulated by interleukin-5 (IL-5). To examine the effect of chronic IL-5 exposure on hematopoiesis, IL-5 transgenic (IL-5trg) mice and wild type BALB/c (WT) mice were examined. In comparison to WT mice, a significant alteration in bone marrow hematopoiesis was observed in IL-5trg mice. While the total number of myeloid progenitors in the bone marrow of IL-5trg mice was not significantly altered, the number of long term culture initiating cells (LTC-IC) was 1.5-fold lower than those observed in WT mice. Furthermore, IL-5trg mice failed to demonstrate hematopoietic activity in long-term bone marrow cultures, which correlated with a significant decrease in the number of bone marrow mesenchymal/stromal progenitor cells (MSP) in these mice. In comparison to WT mice, a 10-fold decrease was observed in the number of fibroblast colony forming units (CFU-F) in IL-5trg bone marrow. Hematopoietic activity of IL-5trg bone marrow cells was rescued by cultivation on pre-established layers of bone marrow-derived stromal cells. However, In contrast to bone marrow, increased hematopoietic activity was observed in the spleen and peripheral blood of IL-5trg mice. Likewise, the numbers of LTC-IC and granulocyte-macrophage, macrophage, eosinophil, B-lymphocyte progenitors in the peripheral blood and spleen of IL-5trg mice were ~20 fold higher than in WT mice. A significant increase in CFU-F numbers was also observed in the spleens of IL-5trg compared to WT mice. Overall, our results suggest that constitutive over-expression of IL-5 can potentially induce colonization of spleen with MSP, which provides the necessary microenvironment for establishment of hematopoiesis in extramedullary sites.
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