Uticaj sistemske administracije lipopolisaharida na strukturne, celularne i molekularne karakteristike slezine miša
The impact of systemic administration of lipopolysaccharide on structural, cellular and molecular characteristics of the mouse spleen.
Докторанд
Lalić, Ivana M.Ментор
Milićević, NovicaЧланови комисије
Bumbaširević, VladimirPopadić, Dušan
Čolić, Miodrag
Метаподаци
Приказ свих података о дисертацијиСажетак
Lipopolisaharid (LPS) je glavna komponenta spoljašnje membrane Gram
negativnih bakterija. Prepoznavanje LPS-a inicira intracelularne signalne puteve koji
dovode do transkripcije gena i oslobaĊanja proinflamatornih medijatora. Dobro je
poznato da kljuĉnu ulogu u imunskom odgovoru na LPS ima receptor TNFR1 (tumor
necrosis factor receptor-1), kao i da TNFR1-/- (tumor necrosis factor receptor-1
knockout) miševi pokazuju rezistenciju na endotoksiĉni šok ĉak i nakon tretmana
letalnim dozama LPS-a. Dosadašnja istraţivanja su pokazala da LPS izaziva migraciju
nekoliko ćelijskih tipova unutar slezine. MeĊutim, nema podataka o uticaju LPS-a na
populaciju B i T limfocita koji se nalaze u crvenoj pulpi slezine miša. Nedavna studija
istakla je znaĉaj hemokina CCL20 u brzoj akumulaciji B limfocita u slezini miša nakon
sistemske administracije Nod1 agoniste, koji izaziva sistemsku inflamaciju in vivo.
Cilj: Ispitivanje uticaja sistemske administracije LPS-a na broj B i T limfocita u
crvenoj pulpi sle...zine miša, kao i na strukturnu organizaciju bele pulpe slezine, 24 h
nakon tretmana. Osim toga, cilj ove studije bio je da ispita uticaj sistemske
administracije LPS-a na ekspresiju gena za hemokine i proinflamatorne citokine u
slezini miša 1 h, 2 h i 24 h nakon tretmana. Dodatni cilj bio je da se ispitaju potencijalne
promene u ekspresiji hemokina CCL20 u slezini miša 2 h nakon sistemske
administracije LPS-a, kao i da se odredi lokalizacija ćelija koje bi u ovim uslovima
proizvodile CCL20.
Materijal i metode: Eksperimenti su izvoĊeni na wild-type miševima soja C57BL/6 i
TNFR1-/- miševima istog soja. Za ispitivanje uticaja sistemske administracije LPS-a na
broj B i T limfocita u crvenoj pulpi slezine, kao i na strukturnu organizaciju bele pulpe
slezine, formirane su ĉetiri grupe ţivotinja: netretirani wild-type miševi (n=5), tretirani
wild-type miševi (n=5), netretirani TNFR1-/- miševi (n=5) i tretirani TNFR1-/- miševi
(n=5). Tretman ţivotinja podrazumevao je ubrizgavanje u repnu venu LPS-a E. coli (soj
055:B5) rastvorenog u fosfatnom puferu, u dozi 2,5 μg/g telesne mase...
Lipopolysaccharide (LPS) is a major component of the outer membrane
of Gram negative bacteria. Recognition of LPS initiates intracellular signaling pathways
which lead to gene transcription and release of proinflammatory mediators. It is well
known that the key role in the immune response to LPS has the receptor TNFR1 (tumor
necrosis factor receptor-1) and that TNFR1-/- (tumor necrosis factor receptor-1
knockout) mice show resistance to endotoxic shock even after treatment with lethal
doses of LPS. Previous research has shown that LPS causes migration of several cell
types within the spleen. However, there is no data on the effect of LPS on the
population of B and T lymphocytes found in the red pulp of the mouse spleen. A recent
study highlighted the importance of chemokine CCL20 in the rapid accumulation of B
lymphocytes in the mouse spleen after systemic administration of Nod1 agonist, which
induces systemic inflammation in vivo.
Aim: Examination of the effects of systemic administra...tion of LPS on the number of B
and T lymphocytes in the red pulp of the mouse spleen, as well as on the structural
organization of the white pulp of the spleen, 24 hours after treatment. In addition, the
aim of this study was to examine the effect of systemic administration of LPS on the
expression of genes for chemokines and proinflammatory cytokines in the mouse spleen
1 h, 2 h, and 24 h after treatment. An additional goal was to investigate the potential
changes in the expression of chemokine CCL20 in the mouse spleen 2 h after systemic
administration of LPS, and to determine the localization of cells that might produce
CCL20 in these conditions.
Material and methods: The experiments were performed on C57BL/6 wild-type and
TNFR1-/- mice. In order to examine the effects of systemic administration of LPS on the
number of B and T lymphocytes in the red pulp of the spleen, as well as on the
structural organization of the splenic white pulp, four groups of animals were formed:
untreated wild-type mice (n = 5), treated wild-type mice (n = 5), untreated TNFR1-/-
mice (n = 5) and treated TNFR1-/- mice (n = 5)...
Факултет:
Универзитет у Београду, Медицински факултетДатум одбране:
20-09-2018Пројекти:
- Молекуларна регулација структурне организације лимфатичних органа (RS-MESTD-Basic Research (BR or ON)-175005)