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Granulocyte Macrophage–Colony-Stimulating Factor-Dependent Proliferation Is Impaired in Macrophages From Senescence-Accelerated Mice

¹ Macrophage Biology Group, Institute for Research in Biomedicine, and Department of Physiology, University of Barcelona, Spain.
² Unit of Pharmacology, School of Medicine and Health Sciences, Rovira i Virgili University, Reus, Spain.

Address correspondence to Jorge Lloberas, PhD, Institute for Research in Biomedicine, Barcelona, Barcelona Science Park, C/ Josep Samitier 1-5, E-08028 Barcelona, Spain. E-mail: jlloberas{at}ub.edu

A senescence-accelerated (SAMP8) mouse model was used to determine the effect of aging on the immune system. We produced in vitro bone marrow-derived macrophages from SAMP8 mice and compared them against senescence-resistant, long-lived mice (SAMR1). Although macrophages from both strains of mice proliferated in a similar manner in response to monocyte–colony-stimulating factor (M-CSF), SAMP8 macrophages showed an impaired response to granulocyte macrophage–colony-stimulating factor (GM–CSF). Similar levels of external regulated kinases (ERK)1/2 and signaling transducer and activator of transcription 5 (STAT5) phosphorylation were observed in macrophages from both strains of mice. The lack of proliferation was not caused by the induction of apoptosis. Differentiation of bone marrow cells into dendritic cells was similar in both strains of mice, as was the induction of major histocompatibility complex (MHC) class II molecules by interferon-gamma (IFN-). Finally, we determined the density of Langerhans cells in vivo in the skin of the two mouse strains, but no differences were found.

Key Words: Macrophages • Proliferation • Differentiation