Human bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition.
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 cell-to-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 beta 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. Disclosure of potential conflicts of interest is found at the end of this article.
Belaid-Choucair
Zakia
Z
Department of Cytology and Histology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Recherche, University of Liege, Liège, Belgium. mp.defresne@ulg.ac.be
Lepelletier
Yves
Y
Poncin
Géraldine
G
Thiry
Albert
A
Humblet
Chantal
C
Maachi
Mustapha
M
Beaulieu
Aurore
A
Schneider
Elke
E
Briquet
Alexandra
A
Mineur
Pierre
P
Lambert
Charles
C
Mendes-Da-Cruz
Daniella
D
Ahui
Marie Louise
ML
Asnafi
Vahid
V
Dy
Michel
M
Boniver
Jacques
J
Nusgens
Betty V
BV
Hermine
Olivier
O
Defresne
Marie Paule
MP
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018952:Antigens, CD34 / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D017931:DNA Primers; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D039942:Neuropilin-1 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016179:Granulocyte Colony-Stimulating Factor; D039942:Neuropilin-1