Kreutz, Marina and Fritsche, Jana and Ackermann, Ute and Krause, Stefan W. and Andreesen, Reinhard (1998) Retinoic acid inhibits monocyte to macrophage survival and differentiation. BLOOD, 91 (12). pp. 4796-4802. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
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. (C) 1998 by The American Society of Hematology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLONY-STIMULATING FACTOR; M-CSF; TERMINAL DIFFERENTIATION; PROMYELOCYTIC LEUKEMIA; CARBOXYPEPTIDASE-M; MOLECULAR-CLONING; ALL-TRANS; EXPRESSION; CELLS; RECEPTORS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 May 2023 08:36 |
| Last Modified: | 09 May 2023 08:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49736 |
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