期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.02246
关键词
macrophage; monocyte; bone marrow; F4/80; porcine; ADGRE1/EMR1; adhesion G protein-coupled receptor E1
类别
资金
- Biotechnology and Biological Sciences Research Council (BBSRC), UK [BB/L001209/1, BB/L004623/1]
- Medical Research Council, UK [MR/M019969/1]
- Mater Foundation
- BBSRC [BB/J004227/1, BB/J004235/1, BB/J004243/1, BBS/E/D/20002174, BBS/E/D/10002071]
- Newton Fund
- Horserace Betting Levy Board
- Roslin Foundation
- Biotechnology and Biological Sciences Research Council [BB/L001209/1] Funding Source: researchfish
- BBSRC [BBS/E/D/20002174, BB/L004623/1, BB/L001209/1, BBS/E/D/10002071] Funding Source: UKRI
The F4/80 antigen, encoded by the Adgre1 locus, has been widely-used as a monocyte-macrophage marker in mice, but its value as a macrophage marker in other species is unclear, and has even been questioned. ADGRE1 is a seven transmembrane G protein-coupled receptor with an extracellular domain containing repeated Epidermal Growth Factor (EGF)-like calcium binding domains. Using a new monoclonal antibody, we demonstrated that ADGRE1 is a myeloid differentiation marker in pigs, absent from progenitors in bone marrow, highly-expressed in mature granulocytes, monocytes, and tissue macrophages and induced by macrophage colony-stimulating factor (CSF1) treatment in vivo. Based upon these observations, we utilized RNA-Seq to assess the expression of ADGRE1 mRNA in bone marrow or monocyte-derived macrophages (MDM) and alveolar macrophages from 8 mammalian species including pig, human, rat, sheep, goat, cow, water buffalo, and horse. ADGRE1 mRNA was expressed by macrophages in each species, with inter-species variation both in expression level and response to lipopolysaccharide (LPS) stimulation. Analysis of the RNA-Seq data also revealed additional exons in several species compared to current Ensembl annotations. The ruminant species and horses appear to encode a complete duplication of the 7 EGF-like domains. In every species, Sashimi plots revealed evidence of exon skipping of the EGF-like domains, which are highly-variable between species and polymorphic in humans. Consistent with these expression patterns, key elements of the promoter and a putative enhancer are also conserved across all species. The rapid evolution of this molecule and related ADGRE family members suggests immune selection and a role in pathogen recognition.
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