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dc.creatorDimitrijević, Mirjana
dc.creatorStanojević, Stanislava
dc.creatorBlagojević, Veljko
dc.creatorCuruvija, Ivana
dc.creatorVujnović, Ivana
dc.creatorPetrović, Raisa
dc.creatorArsenović-Ranin, Nevena
dc.creatorVujić, Vesna
dc.creatorLeposavić, Gordana
dc.date.accessioned2019-09-02T11:52:33Z
dc.date.available2019-09-02T11:52:33Z
dc.date.issued2016
dc.identifier.issn1389-5729
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2609
dc.description.abstractMacrophages 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.en
dc.publisherSpringer, New York
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175050/RS//
dc.rightsrestrictedAccess
dc.sourceBiogerontology
dc.titleAging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4en
dc.typearticle
dc.rights.licenseARR
dcterms.abstractAрсеновић-Ранин, Невена; Благојевић, Вељко; Станојевић, Станислава; Цурувија, Ивана; Вујновић, Ивана; Петровић, Раиса; Димитријевић, Мирјана; Вујић, Весна; Лепосавић, Гордана;
dc.citation.volume17
dc.citation.issue2
dc.citation.spage359
dc.citation.epage371
dc.citation.other17(2): 359-371
dc.citation.rankM22
dc.identifier.wos000373298800009
dc.identifier.doi10.1007/s10522-015-9620-x
dc.identifier.pmid26463212
dc.identifier.scopus2-s2.0-84944518727
dc.identifier.rcubconv_3530
dc.type.versionpublishedVersion


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