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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Haematologica
2015 ; 100
(2
): 178-87
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Dexamethasone targeted directly to macrophages induces macrophage niches that
promote erythroid expansion
#MMPMID25533803
Falchi M
; Varricchio L
; Martelli F
; Masiello F
; Federici G
; Zingariello M
; Girelli G
; Whitsett C
; Petricoin EF 3rd
; Moestrup SK
; Zeuner A
; Migliaccio AR
Haematologica
2015[Feb]; 100
(2
): 178-87
PMID25533803
show ga
Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus
dexamethasone, a model for stress erythropoiesis, generate numerous erythroid
cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169).
Interactions occurring between erythroblasts and macrophages in these cultures
and the biological effects associated with these interactions were documented by
live phase-contrast videomicroscopy. Macrophages expressed high motility
interacting with hundreds/thousands of erythroblasts per hour. CD169(pos)
macrophages established multiple rapid 'loose' interactions with proerythroblasts
leading to formation of transient erythroblastic island-like structures. By
contrast, CD169(neg) macrophages established 'tight' interactions with mature
erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos)
macrophages were associated with proerythroblast cytokinesis (the M phase of the
cell cycle) suggesting that these interactions may promote proerythroblast
duplication. This hypothesis was tested by experiments that showed that as few as
103 macrophages significantly increased levels of
3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide incorporation
frequency in S/G2/M and cytokinesis expressed by proerythroblasts over 24 h of
culture. These effects were observed also when macrophages were co-cultured with
dexamethasone directly conjugated to a macrophage-specific CD163 antibody. In
conclusion, in addition to promoting proerythroblast proliferation directly,
dexamethasone stimulates expansion of these cells indirectly by stimulating
maturation and cytokinesis supporting activity of macrophages.