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,1,12
* Departament de Fisiologia (Biologia del Macròfag) and Fundació August Pi i Sunyer, Campus de Bellvitge; and
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028 Barcelona, Spain
2Correspondence: Laboratori de Fisiologia Molecular, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Avda. Diagonal 645, E-08028 Barcelona, Spain. E-mail: afelipe{at}porthos.bio.ub.es
To evaluate the mechanisms involved in macrophage proliferation and
activation, we studied the regulation of the nucleoside transport
systems. In murine bone marrow-derived macrophages, the nucleosides
required for DNA and RNA synthesis are recruited from the extracellular
medium. M-CSF induced macrophage proliferation and DNA and RNA
synthesis, whereas interferon 
(IFN-) led to activation, blocked
proliferation, and induced only RNA synthesis. Macrophages express at
least the concentrative systems N1 and N2 (CNT2 and CNT1 genes,
respectively) and the equilibrative systems es and
ei (ENT1 and ENT2 genes, respectively). Incubation with
M-CSF only up-regulated the equilibrative system es.
Inhibition of this transport system blocked M-CSF-dependent
proliferation. Treatment with IFN- only induced the concentrative N1
and N2 systems. IFN- also down-regulated the increased expression of
the es equilibrative system induced by M-CSF. Thus,
macrophage proliferation and activation require selective regulation of
nucleoside transporters and may respond to specific requirements for
DNA and RNA synthesis. This report also shows that the nucleoside
transporters are critical for macrophage proliferation and
activation.—Soler, C., García-Manteiga, J., Valdés, R.,
Xaus, J., Comalada, M., Casado, F. J., Pastor-Anglada, M., Celada,
A., Felipe, A. Macrophages require different nucleoside transport
systems for proliferation and activation.
Key Words: nucleoside uptake • interferon • macrophage colony-stimulating factor
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