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 C57Bl/6 mice. The accumulation of
cholesterol, the change of
cytokine production,
PPAR-γ activity and
cholesterol efflux in macrophages of C57Bl/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 resoluti- on 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.