Macrophage-specific gene functions in Spi1-directed innate immunity

作者：Zakrzewska Anna; Cui Chao; Stockhammer Oliver W; Benard Erica L; Spaink Herman P; Meijer Annemarie H^*

来源：Blood, 2010, 116(3): E1-E11.

DOI：10.1182/blood-2010-01-262873

The Spi1/Pu.1 transcription factor plays a crucial role in myeloid cell development in vertebrates. Despite extensive studies of Spi1, the controlled gene group remains
largely unknown. To identify genes dependent on Spi1, we used a microarray strategy using a knockdown approach in zebrafish embryos combined with fluorescence-activated cell sorting of myeloid cells from transgenic embryos. This approach of using knockdowns
with specific green fluorescent
protein-marked cell types was highly
successful in identifying macrophage-specific
genes in Spi1-directed innate immunity. We found a gene group downregulated
on spi1 knockdown, which is also enriched in fluorescence-activated
cell-sorted embryonic myeloid cells of a spi1:GFP transgenic line. This gene
group, representing putative myeloidspecific Spi1 target genes, contained all 5 previously identified Spi1-dependent zebrafish genes as well as a large set of novel immune-related genes. Colocalization studies with neutrophil and macrophage markers revealed that genes cxcr3.2, mpeg1, ptpn6, and mfap4 were expressed specifically in early embryonic
macrophages. In a functional approach,
we demonstrated that gene cxcr3.2, coding for chemokine receptor 3.2, is involved in macrophage migration
to the site of bacterial infection.
Therefore, based on our combined transcriptome analyses, we discovered
novel early macrophage-specific marker
genes, including a signal transducer
pivotal for macrophage migration in
the innate immune response. (Blood.
2010;116(3):e1-e11)

• 出版日期2010-7-22