Gene microarray analysis reveals interleukin-5-dependent transcriptional targets in mouse bone marrow.
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.
Byström
Jonas
J
NIAID, NIH, Bldg 10, Rm 11N104, 9000 Rockville Pike, Bethesda, MD, 20892, USA. jbystrom@niaid.nih.gov
Wynn
Thomas A
TA
Domachowske
Joseph B
JB
Rosenberg
Helene F
HF
D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D047091:Eosinophil Granule Proteins; D004802:Eosinophilia / Q000209:etiology; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000235:genetics; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic
D001798:Blood Proteins; D018076:DNA, Complementary; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D012260:Ribonucleases