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Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4

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Abstract

Macrophages undergo significant functional alterations during aging. The aim of the present study was to investigate changes of rat macrophage functions and response to M1/M2 polarization signals with age. Therefore, resident and thioglycollate-elicited peritoneal macrophages from young (3-month-old) and aged (18–19-month-old) rats were tested for phagocytic capacity and ability to secrete inflammatory mediators following in vitro stimulation with LPS and GM-CSF, and IL-4, prototypic stimulators for classically (M1) and alternatively activated (M2) macrophages, respectively. Aging increased the frequency of monocyte-derived (CCR7+ CD68+) and the most mature (CD163+ CD68+) macrophages within resident and thioglycollate-elicited peritoneal macrophages, respectively. The ability to phagocyte zymosan of none of these two cell subsets was affected by either LPS and GM-CSF or IL-4. The upregulated production of IL-1β, IL-6 and IL-10 and downregulated that of TGF-β was observed in response to LPS in resident and thioglycollate-elicited macrophages from rats of both ages. GM-CSF elevated production of IL-1β and IL-6 in resident macrophages from aged rats and in thioglycollate-elicited macrophages from young rats. Unexpectedly, IL-4 augmented production of proinflammatory mediators, IL-1β and IL-6, in resident macrophages from aged rats. In both resident and thioglycollate-elicited macrophages aging decreased NO/urea ratio, whereas LPS but not GM-SCF, shifted this ratio toward NO in the macrophages from animals of both ages. Conversely, IL-4 reduced NO/urea ratio in resident and thioglycollate-elicited macrophages from young rats only. In conclusion, our study showed that aging diminished GM-CSF-triggered polarization of elicited macrophages and caused paradoxical IL-4-driven polarization of resident macrophages toward proinflammatory M1 phenotype. This age-related deregulation of macrophage inflammatory mediator secretion and phagocytosis in response to M1/M2 activators may lead to the deficient control of infectious and/or inflammatory diseases in advanced age.

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Acknowledgments

Supported by Ministry of Education, Science and Technological Development Republic of Serbia, Grant No 175050.

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Authors and Affiliations

  1. Department of Immunology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Despota Stefana 142, Belgrade, Serbia

    Mirjana Dimitrijević

  2. Immunology Research Center “Branislav Janković”, Institute of Virology, Vaccines and Sera, “Torlak”, Vojvode Stepe 458, Belgrade, 11152, Serbia

    Stanislava Stanojević, Veljko Blagojević, Ivana Ćuruvija, Ivana Vujnović & Raisa Petrović

  3. Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia

    Nevena Arsenović-Ranin

  4. Institute of Chemistry in Medicine, School of Medicine, University of Belgrade, Višegradska 26, Belgrade, 11000, Serbia

    Vesna Vujić

  5. Department of Physiology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia

    Gordana Leposavić

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  1. Mirjana Dimitrijević
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  2. Stanislava Stanojević
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Dimitrijević, M., Stanojević, S., Blagojević, V. et al. Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4. Biogerontology 17, 359–371 (2016). https://doi.org/10.1007/s10522-015-9620-x

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