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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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.
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Biogerontology, 2016, 17, 2, 359-371Publisher:
- Springer, New York
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DOI: 10.1007/s10522-015-9620-x
ISSN: 1389-5729
PubMed: 26463212
WoS: 000373298800009
Scopus: 2-s2.0-84944518727
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PharmacyTY - JOUR AU - Dimitrijević, Mirjana AU - Stanojević, Stanislava AU - Blagojević, Veljko AU - Curuvija, Ivana AU - Vujnović, Ivana AU - Petrović, Raisa AU - Arsenović-Ranin, Nevena AU - Vujić, Vesna AU - Leposavić, Gordana PY - 2016 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2609 AB - 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 response 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. PB - Springer, New York T2 - Biogerontology T1 - Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4 VL - 17 IS - 2 SP - 359 EP - 371 DO - 10.1007/s10522-015-9620-x ER -
@article{ author = "Dimitrijević, Mirjana and Stanojević, Stanislava and Blagojević, Veljko and Curuvija, Ivana and Vujnović, Ivana and Petrović, Raisa and Arsenović-Ranin, Nevena and Vujić, Vesna and Leposavić, Gordana", year = "2016", 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 response 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.", publisher = "Springer, New York", journal = "Biogerontology", title = "Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4", volume = "17", number = "2", pages = "359-371", doi = "10.1007/s10522-015-9620-x" }
Dimitrijević, M., Stanojević, S., Blagojević, V., Curuvija, I., Vujnović, I., Petrović, R., Arsenović-Ranin, N., Vujić, V.,& Leposavić, G.. (2016). Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4. in Biogerontology Springer, New York., 17(2), 359-371. https://doi.org/10.1007/s10522-015-9620-x
Dimitrijević M, Stanojević S, Blagojević V, Curuvija I, Vujnović I, Petrović R, Arsenović-Ranin N, Vujić V, Leposavić G. Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4. in Biogerontology. 2016;17(2):359-371. doi:10.1007/s10522-015-9620-x .
Dimitrijević, Mirjana, Stanojević, Stanislava, Blagojević, Veljko, Curuvija, Ivana, Vujnović, Ivana, Petrović, Raisa, Arsenović-Ranin, Nevena, Vujić, Vesna, Leposavić, Gordana, "Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4" in Biogerontology, 17, no. 2 (2016):359-371, https://doi.org/10.1007/s10522-015-9620-x . .