INFLUENCE OF CHOLESTEROL ON MACROPHAGE FOAM CELLS FORMATION
AT ZYMOSAN-INDUCED INFLAMMATION OF MICE
O.M. Dolganova,1,* M.I. Rudina,1 M.V. Chrapova,2 M.I. Dushkin 2
1 Institute of Internal and Preventive Medicine SB RAMS and
2 State Research Institute of Physiology and Fundamental Medicine RAMS, Novosibirsk;
* e-mail: Kh_Olgam@mail.ru
It has been shown recently that significant number (to 40 % from total population) of macrophage foam
cells (MFC) is formed during early time (24 h) of zymosan-induced peritonitis resolution and agonists of peroxisome
proliferation activated receptors-α, -γ (PPAR-α, -γ) exert anti-inflammatory action, protecting their formation
(Dushkin et al., 2007). The work is devoted to investigate of the influence of cholesterol-containing liposomes
(CHL) on dinamic of zimozan-induced peritonitis in C57B1/6 mice. The accumulation of cholesterol,
the change of cytokine production, PPAR-g activity and cholesterol efflux in macrophages of C57B1/6 mice
has been investigated. The infiltration of neutrophils, amounts of mononuclear cells and MFC formation were
significantly increased in peritonel cavity of zymosan-induced mice that led to in expansion of the period of inflammatory
resolution and of the period of MFC resolution. If macrophages obtained after zymosan injection
mainly accumulated triglycerides (TG) and at high speed incorporated [1-14C]oleate into TG, the injection of
CHL after zymosan-indused inflammation lead to dramatic promotion MFC containing primarily free cholesterol
and Ch ethers and been aggravation of [1-14C]oleate incorporation into cholesterol ethers in macrophages (mainly
for 2 days). It has to shown that CHL against a background of inflammation promoted reduction of fluorescent
NBD-cholesterol efflux from macrophages throughout the studied period (5 days) whereas zymosan inhibited
cholesterol efflux at the early stages of inflammation (1 and 2 days), then, on 3ed day, the cholesterol
efflux was recovered and increased on day 5. At the same time CHL stimulated the production of TNFα and
TGFβ and inhibited the production of IL-10 and DNA-binding activity of PPAR-γ macrophages obtained at
early as well as late stages of zymosan-induced peritonitis (compared with injection zymosan only). Thus, accumulation
of cholesterol in inflammatory macrophages and promotion of MFC formation prolog timely resolution
of acute inflammation inducing alteration of pro- and anti-inflammatory cytokine balance and evoking the
repression of macrophage DNA-binding activity of PPAR-γ and cholesterol efflux.
Key words: macrophage foam cells, inflammation, cholesterol, cytokines, PPAR-γ
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