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 Blood, 1 February 2004, Vol. 103, No. 3, pp. 868-877.
Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-08-2778.

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HEMATOPOIESIS

Gene microarray analysis reveals interleukin-5–dependent transcriptional targets in mouse bone marrow

Jonas Byström, Thomas A. Wynn, Joseph B. Domachowske, and Helene F. Rosenberg

From the Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD; Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD; Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, NY.

Interleukin-5 (IL-5) is a hematopoietic differentiation factor that promotes the development of mature eosinophils from progenitors in bone marrow. We present a multifactorial microarray study documenting the transcriptional events in bone marrow of wild-type and IL-5–deficient mice at baseline and in response to infection with Schistosoma mansoni. The microarray data were analyzed by a 4-way subtractive algorithm that eliminated confounding non-IL-5–related sequelae of schistosome infection as well as alterations in gene expression among uninfected mice. Among the most prominent findings, we observed 7- to 40-fold increased expression of transcripts encoding the classic eosinophil granule proteins (eosinophil peroxidase, major basic protein, the ribonucleases) together with arachidonate-15-lipoxygenase and protease inhibitor plasminogen activator inhibitor 2 (PAI-2), in the IL-5–producing, infected wild-type mice only. This was accompanied by increased transcription of genes involved in secretory protein biosynthesis and granule-vesicle formation. Interestingly, we did not detect increased expression of genes encoding eosinophil-related chemokine receptors (CCR1, CCR3) or members of the GATA or CCAAT/enhancer binding protein (C/EBP) transcription factor families. These data suggest that the IL-5–responsive progenitors in the mouse bone marrow are already significantly committed to the eosinophil lineage and that IL-5 promotes differentiation of these committed progenitors into cells with recognizable and characteristic cytoplasmic granules and granule proteins.


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