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Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with the development of the myeloid
1Department of Pathology, Howard Hughes Medical Institute, Stanford University School of Medicine, CA 94305.
Abstract:
MRP8 and MRP14 are two S100-like calcium-binding proteins of unknown function, associated with numbers of human inflammatory disorders. Both molecules have been described as L1 complex, cystic fibrosis antigen, or p8 and p14. We report here the cloning of mouse MRP8 and MRP14 and their pattern of expression during hematopoiesis. Mouse MRP8 and MRP14 proteins share 59% identity with their human counterparts, but they are more divergent than the other members of the S100 protein family. Mouse MRP proteins are coexpressed in fetal myeloid progenitors, where they are detected as early as day 11 of gestation. In fetal liver and yolk sac, MRP+ cell populations increased in number, in association with the development of the myeloid lineage. In adult mouse, we identified MRP8 and MRP14 proteins in immature myeloid cells of the bone marrow, myeloid cells in the splenic red pulp and marginal zone, in addition to monocytes and blood neutrophils. However, MRP expression is lost as cells terminally differentiate into tissue macrophages. In addition, using thioglycollate-induced peritoneal inflammatory exudates, we showed that MRP8 and MRP14 proteins are highly expressed in recruited neutrophils and monocytes.
Insights
Mouse myeloid progenitor cells express MRP8 and MRP14 proteins, crucial for inflammatory disorders. These calcium-binding proteins are found in immature myeloid cells but are lost during terminal differentiation into macrophages.
Area of Science:
- Immunology
- Molecular Biology
- Hematopoiesis
Background:
- MRP8 and MRP14 are S100-like calcium-binding proteins implicated in human inflammatory disorders.
- Their precise function and expression patterns, particularly during hematopoiesis, remain largely unknown.
Purpose of the Study:
- To clone mouse MRP8 and MRP14 and characterize their expression patterns during hematopoiesis.
- To investigate the role of MRP8 and MRP14 in myeloid cell development and inflammatory responses.
Main Methods:
- Cloning of mouse MRP8 and MRP14 genes.
- Analysis of protein expression via immunohistochemistry and flow cytometry.
- Investigation of expression in fetal and adult hematopoietic tissues, including bone marrow, fetal liver, and spleen.
- Examination of expression in thioglycollate-induced peritoneal inflammatory exudates.
Main Results:
- Mouse MRP8 and MRP14 share 59% identity with human counterparts and are coexpressed in fetal myeloid progenitors by day 11 of gestation.
- MRP+ cell populations increase with myeloid lineage development in fetal liver and yolk sac.
- In adult mice, MRP8 and MRP14 are found in immature myeloid cells, monocytes, and neutrophils, but not in terminally differentiated macrophages.
- Expression is significantly upregulated in neutrophils and monocytes recruited to inflammatory sites.
Conclusions:
- MRP8 and MRP14 are key molecular markers of immature myeloid cells and inflammatory infiltrates in mice.
- Their expression dynamics suggest a role in myeloid cell development and inflammatory processes.
- Understanding MRP8/MRP14 expression provides insights into the cellular mechanisms underlying inflammatory disorders.
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