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

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2016
Authors
Dimitrijević, Mirjana
Stanojević, Stanislava
Blagojević, Veljko
Curuvija, Ivana
Vujnović, Ivana
Petrović, Raisa
Arsenović-Ranin, Nevena
Vujić, Vesna
Leposavić, Gordana
Article (Published version)
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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-1 beta, IL-6 and IL-10 and downregulated that of TGF-beta was observed in resp...onse to LPS in resident and thioglycollate-elicited macrophages from rats of both ages. GM-CSF elevated production of IL-1 beta 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-1 beta 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.

Source:
Biogerontology, 2016, 17, 2, 359-371
Publisher:
  • Springer, New York
Projects:
  • Immune system plasticity during aging: Immunomodulatory capacity of oestrogens (RS-175050)

DOI: 10.1007/s10522-015-9620-x

ISSN: 1389-5729

PubMed: 26463212

WoS: 000373298800009

Scopus: 2-s2.0-84944518727
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/2609
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  • Radovi istraživača / Researchers’ publications
Institution
Pharmacy

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