Starenje se povezuje sa razvojem sistemskog, sterilnog hroničnog zapaljenja (engl.
„inflammaging”). Malo je podataka o uticaju genetskih faktora i pola na sposobnost makrofaga
(Mφ), kao ključnih ćelija urođenog imunskog odgovora, da tokom starenja “kontrolišu”
rezoluciju akutnog zapaljenja i time razvoj hroničnog zapaljenja. Ciljevi ove disertacije su bili
da se ispita 1) uticaj rane faze reproduktivnog starenja na fenotipske osobine (ekspresija
markera povezanih sa aktivacijom i poreklom/funkcijom) i funkcijska svojstva (fagocitoza,
sinteza inflamatornih medijatora) Mφ “mirne” i inflamirane (delovanjem tioglikolata)
peritonealne duplje ženki Albino Oxford (AO) pacova, 2) značaj genetskih faktora za
reproduktivnim starenjem uslovljene promene peritonealnih Mφ od značaja za uspešnu
rezoluciju akutnog zapaljenja i 3) uloga polnih steroida u nastanku ovih promena uporednom
analizom promena kod mužjaka i ženki AO pacova, njihovom analizom kod ženki AO pacova
kojima su na kraju reproduktivnog perioda uklonjeni jajnici i ispitivanjem delovanja
estradiola na Mφ mladih i sredovečnih ženki AO pacova in vitro. Rezultati su pokazali da: 1) se
sposobnost Mφ ženki AO pacova da “kontrolišu” rezoluciju akutnog zapaljenja menja već
tokom rane faze reproduktivnog starenja, kao i da su ove promene sojno specifične (Mφ
sredovečnih ženki AO pacova koje “uspešnije” stare od ženki Dark Agouti pacova pokazuju
svojstva koja se mogu povezati sa boljom “kontrolom” inflamacije); 2) su ove promene polno
specifične (Mφ sredovečnih ženki imaju svojstva koja ukazuju na veći kapacitet da
“kontrolišu” inflamaciju od Mφ mužjaka istog uzrasta) i 3) u nastanku promena relevantnih za
sposobnost Mφ ženki AO pacova da “kontrolišu” akutnu inflamaciju važnu ulogu imaju
promene u delovanju i estradiola i progesterona. Dodatno, ispitavanja in vitro su ukazala da su
za uzrasno zavisne promene u sposobnosti Mφ da “kontrolišu” inflamaciju pored promene u
koncentraciji estradiola važne i one u samim Mφ, koje menjaju njihov odgovor na delovanje
estradiola.Aging is associated with the development of systemic, sterile chronic inflammation
("inflammaging"). Little is known about the influence of genetic factors and sex on the ability
of macrophages (Mφ), as key innate immune cells, to "control" the resolution of acute
inflammation and thus the development of chronic inflammation during aging. The objectives
of this dissertation were to examine 1) the influence of the early phase of reproductive aging
on phenotypic characteristics (expression of markers associated with activation and
origin/function) and functional characteristics (phagocytosis, synthesis of inflammatory
mediators) of Mφ isolated from “naive” and inflamed (thioglycollate-induced) peritoneal
cavity of females Albino Oxford (AO) rats; 2) the significance of genetic factors for
reproductive aging-related changes of peritoneal Mφ, especially those important for
successful resolution of acute inflammation and 3) the role of sex steroids in the occurrence of
these changes by comparative analysis in males and females of AO rats, their analysis in
female AO rats whose ovaries were removed at the end of the reproductive period and by
examining in vitro effect of estradiol on Mφ from young and middle-aged female AO rats. The
results showed that: 1) the ability of Mφ from AO females to “control” the resolution of acute
inflammation changes during the early phase of reproductive aging, and these changes are
strain-specific (Mφ from middle-aged AO females that “age more successful” than Dark Agouti
females, show properties which may be associated with better "control" of inflammation); 2)
these changes are sex-specific (Mφ from middle-aged females have a greater capacity to
“control” inflammation than Mφ from males of the same age group) and 3) both estradiol and
progesterone play important roles in the ability of Mφ from AO females to “control” acute
inflammation. In vitro studies revealed that, in addition to changes in estradiol concentration,
intrinsic changes in Mφ that regulate their response to estradiol action are important for age-
dependent changes in Mφ ability to „control“ inflammation
