title: Constitutive overexpression of IL-5 induces extramedullary hematopoiesis in the spleen.
abstract: 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.
authors.affiliation: Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Khaldoyanidi
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Sikora
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: P
authors.initials: P
authors.lastname: Sriramarao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D015848:Interleukin-5