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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-03-0735.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 863-868
HEMATOPOIESIS
Constitutive overexpression of IL-5 induces extramedullary
hematopoiesis in the spleen
Sophia Khaldoyanidi,
Lyudmila Sikora,
David H. Broide,
Marc E. Rothenberg, and
P. Sriramarao
From the Division of Vascular Biology, La Jolla
Institute for Molecular Medicine, San Diego, CA; Department of
Medicine, University of California San Diego, La Jolla; Division of
Allergy and Immunology, Department of Pediatrics, Children's Hospital
Medical Center, Cincinnati, OH.
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. Although 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-ICs) was
1.5-fold lower than that 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 (MSP) cells in these mice.
In comparison to WT mice, a 10-fold decrease was observed in the number
of fibroblast colony-forming units (CFU-Fs) in IL-5trg bone marrow.
Hematopoietic activity of IL-5trg bone marrow cells was rescued by
cultivation on preestablished 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-ICs and granulocyte-macrophage,
macrophage, eosinophil, B-lymphocyte progenitors in the peripheral
blood and spleen of IL-5trg mice were approximately 20-fold higher than in WT mice. A significant increase in CFU-F numbers was also observed in the spleens of IL-5trg mice compared with WT mice. Overall, our
results suggest that constitutive overexpression of IL-5 can potentially induce colonization of spleen with MSP cells, which provides the necessary microenvironment for establishment of
hematopoiesis in extramedullary sites.
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