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- Title
Human Bone Marrow Adipocytes Block Granulopoiesis Through Neuropilin-1-Induced Granulocyte Colony-Stimulating Factor Inhibition.
- Authors
Belaid-Choucair, Zakia; Lepelletier, Yves; Poncin, Géraldine; Thiry, Albert; Humblet, Chantal; Maachi, Mustapha; Beaulieu, Aurore; Schneider, Elke; Briquet, Alexandra; Mineur, Pierre; Lambert, Charles; Mendes-Da-Cruz, Daniella; Ahui, Marie Louise; Asnafi, Vahid; Dy, Michel; Boniver, Jacques; Nusgens, Betty V.; Hermine, Olivier; Defresne, Marie Paule
- Abstract
Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral bone marrow (BM) coincides with increased expression of neuropilin-1 (NP-1), while it is weakly expressed in hematopoietic iliac crest BM. Starting from this observation, we postulated that adipocytes might exert a negative effect on hematopoiesis mediated through NP-1. To test this hypothesis, we set up BM adipocytes differentiated into fibroblast-like fat cells (FLFC), which share the major characteristics of primitive unilocular fat cells, as an experimental model. As expected, FLFCs constitutively produced macrophage colony stimulating factor and induced CD34+ differentiation into macrophages independently of cell-to-cell contact. By contrast, granulopoiesis was hampered by cellto- cell contact but could be restored in transwell culture conditions, together with granulocyte colony stimulating factor production. Both functions were also recovered when FLFCs cultured in contact with CD34+ cells were treated with an antibody neutralizing NP-1, which proved its critical implication in contact inhibition. An inflammatory cytokine such as interleukin-1 β or dexamethasone modulates FLFC properties to restore granulopoiesis. Our data provide the first evidence that primary adipocytes exert regulatory functions during hematopoiesis that might be implicated in some pathological processes.
- Subjects
BONE marrow; FAT cells; CELLULAR control mechanisms; KILLER cells; CELL division; CELLULAR immunity; IMMUNE system; ADIPOSE tissues
- Publication
Stem Cells, 2008, Vol 26, Issue 6, p1556
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1634/stemcells.2008-0068