|
|
 Previous Article | Table of Contents | Next Article 
Retinoic Acid Inhibits Monocyte to Macrophage Survival and
Differentiation
Marina Kreutz,
Jana Fritsche,
Ute Ackermann,
Stefan W. Krause, and
Reinhard Andreesen
From the Department of Hematology and Oncology, University of
Regensburg, Regensburg, Germany.
Vitamin A metabolites are potent differentiation-inducing agents for
myelomonocytic cell lines in vitro and are successfully used for the
treatment of patients with acute promyelocytic leukemia. However,
little is known about the effects of vitamin A on normal hematopoietic
cells. Therefore, we investigated the effect of vitamin A on
differentiation and activation of human blood monocytes (MO). Culturing
MO for up to 4 days with 9-cis retinoic acid (RA) and all-trans RA but
not retinol reduced MO survival, with the remaining cells being
morphologically comparable to control cells. Because macrophage
colony-stimulating factor (M-CSF) is a well-known survival factor for
MO, we measured the M-CSF content of MO culture supernatants using
enzyme-linked immunosorbent assay and found that RA suppressed the
constitutive secretion of M-CSF. Northern analysis showed that the
M-CSF mRNA expression was only slightly reduced by RA treatment,
suggesting regulation on the posttranscriptional level. In contrast to
MO, M-CSF secretion by MO-derived macrophages (MAC) was not altered by
RA, suggesting a differentiation-dependent switch in the responsiveness
of MO/MAC to RA. Because M-CSF is not only a
survival-promoting but also a differentiation-promoting factor for myeloid cells, we analyzed the effect of RA on MO to MAC
maturation. RA suppressed the expression of the maturation-associated antigen carboxypeptidase M (CPM)/MAX.1 at both the protein and mRNA
levels and modulated the lipopolysaccharide-stimulated
cytokine secretion of MO/MAC. The addition of exogenous M-CSF to
RA-containing MO cultures fails to overcome the RA-induced inhibition
of MO differentiation. However, the survival rate was improved by
exogenous M-CSF. We conclude that RA acts via two different mechanisms
on monocyte survival and differentiation: posttranscriptionally by controlling M-CSF secretion, which decreases MO survival, and transcriptionally regulating the expression of
differentiation-associated genes. The regulation of M-CSF production
may contribute to the antileukemic effect of RA in vivo by reducing
autocrine M-CSF production by leukemic cells.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4796-4802
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. Zapata-Gonzalez, F. Rueda, J. Petriz, P. Domingo, F. Villarroya, A. de Madariaga, and J. C. Domingo
9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) Ligand, Exerts Immunosuppressive Effects on Dendritic Cells by RXR-Dependent Activation: Inhibition of Peroxisome Proliferator-Activated Receptor {gamma} Blocks Some of the 9cRA Activities, and Precludes Them to Mature Phenotype Development
J. Immunol.,
May 15, 2007;
178(10):
6130 - 6139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Adams, E. Kiss, A. B.V. Arroyo, M. Bonrouhi, Q. Sun, Z. Li, N. Gretz, A. Schnitger, C. C. Zouboulis, M. Wiesel, et al.
13-cis Retinoic Acid Inhibits Development and Progression of Chronic Allograft Nephropathy
Am. J. Pathol.,
July 1, 2005;
167(1):
285 - 298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Babina, K. Mammeri, and B. M. Henz
Retinoic acid up-regulates myeloid ICAM-3 expression and function in a cell-specific fashion--evidence for retinoid signaling pathways in the mast cell lineage
J. Leukoc. Biol.,
March 1, 2001;
69(3):
361 - 372.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. Langstein, J. Michel, and H. Schwarz
CD137 Induces Proliferation and Endomitosis in Monocytes
Blood,
November 1, 1999;
94(9):
3161 - 3168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
