Ccl18/Parc Stimulates Hematopoiesis in Long-term Bone Marrow Cultures Indirectly Through Its Effect on Monocytes.
From: Division of Cancer Biology, Ste 100, La Jolla Institute for Molecular Medicine, 4570 Executive Dr, San Diego, CA 92121, USA.
Blood
- Publish Date: Dec 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 12
- Pages: 3722-9
- Medium: Print
- Language: English
- Citation (JAMA): Wimmer Antonia, Khaldoyanidi Sophia K, Judex Martin, et al. Ccl18/Parc Stimulates Hematopoiesis in Long-term Bone Marrow Cultures Indirectly Through Its Effect on Monocytes.. Blood Dec 2006;108:3722-9
Abstract
Chemokines play a role in regulating hematopoietic stem cell function, including migration, proliferation, and retention. We investigated the involvement of CCL18 in the regulation of bone marrow hematopoiesis. Treatment of human long-term bone marrow cultures (LTBMCs) with CCL18 resulted in significant stimulation of hematopoiesis, as measured by the total number of hematopoietic cells and their committed progenitors produced in culture. Monocytes/macrophages, whose survival was almost doubled in the presence of CCL18 compared with controls, were the primary cells mediating this effect. Conditioned media from CCL18-treated mature monocytes fostered colony-promoting activity that increased the number of colonies formed by hematopoietic progenitor cells. Gene expression profiling of CCL18-stimulated monocytes demonstrated more than 200 differentially expressed genes, including those regulating apoptosis (caspase-8) and proliferation (IL-6, IL-15, stem cell factor [SCF]). Up-regulation of these cytokines was confirmed on the protein expression level. The contribution of SCF and IL-6 in CCL18-mediated stimulatory activity for hematopoiesis was confirmed by SCF- and IL-6-blocking antibodies that significantly inhibited the colony-promoting activity of CCL18-stimulated conditioned medium. In addition to the effect on monocytes, CCL18 facilitated the formation of the adherent layer in LTBMCs and increased the proliferation of stromal fibroblast-like cells.
Mesh Headings (Keywords): Apoptosis, Bone Marrow, Cell Proliferation, Cells, Cultured, Chemokines, CC, Colony-Forming Units Assay, Culture Media, Conditioned, Cytokines, Fibroblasts, Gene Expression Profiling, Hematopoiesis, Humans, Monocytes, Oligonucleotide Array Sequence Analysis, Protein Biosynthesis, Stem Cells, Stromal Cells, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16888095
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