Effects of Oxysterols Upon Macrophage and Lymphocyte Functions In Vitro

Oxygenated derivatives of cholesterol (oxysterols), found in high concentrations in atherosclerotic lesions, are potent immunosuppressive agents inhibiting T-cell responses to different stimuli. The action of oxysterols on macrophage functions and macrophage-lymphocyte interaction has been poorly in...

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Bibliographic Details
Published in:	Prostaglandins & other lipid mediators Vol. 55; no. 4; pp. 219 - 236
Main Authors:	Dushkin, Mikhail, Schwartz, Yakov, Volsky, Nikolaj, Musatov, Mikhail, Vereschagin, Eugeni, Ragino, Julia, Perminova, Olga, Kozlov, Vladimir
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-03-1998
Subjects:	Animals Cholesterol - pharmacology Culture Media, Conditioned - pharmacology Erythrocytes Growth Inhibitors - pharmacology Humans Hydroxycholesterols - pharmacology Immunosuppressive Agents - pharmacology Interleukin-1 - secretion Ketocholesterols - pharmacology Lipopolysaccharides - pharmacology Lymphocyte Activation - drug effects Lymphocyte Culture Test, Mixed lymphocytes Lymphocytes - drug effects Lymphocytes - metabolism Lymphocytes - secretion Macrophage Activation - drug effects Macrophage-Activating Factors - secretion macrophages Macrophages, Peritoneal - drug effects Macrophages, Peritoneal - metabolism Macrophages, Peritoneal - secretion Male Mice Mice, Inbred C57BL Neopterin - secretion Oxysterols Phagocytosis - drug effects Reactive Oxygen Species - metabolism Receptors, Fc - immunology Sheep - blood Spleen - cytology Thymus Gland - cytology macrophages lymphocytes Oxysterols
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Summary:	Oxygenated derivatives of cholesterol (oxysterols), found in high concentrations in atherosclerotic lesions, are potent immunosuppressive agents inhibiting T-cell responses to different stimuli. The action of oxysterols on macrophage functions and macrophage-lymphocyte interaction has been poorly investigated. In this work, the effects of 25-hydroxycholesterol (25-OHCh) and 7-ketocholesterol (7-KCh) upon some functions of murine peritoneal macrophage (PM), such as generation of reactive oxygen intermediates (ROI), secretion of neopterin and interleukin-1 (IL-1)-like activity, Fc-receptor (FcR) activity, and murine and human lymphocyte functions, participating in lymphocyte-macrophage interactions, such as macrophage-activating factor (MAF) and Ia-inducing factor (IaIF) secretion, were studied in vitro. 7-KCh in concentration of 5 μg/mL culture medium only, but not 25-OHCh, significantly inhibited ROI generation by zymosan-stimulated PM. Pretreatment of PM for 22 h with 25-OHCh and 7-KCh led to the decrease of IL-1-like activity secretion. 25-OHCh and 7-KCh inhibited both FcR-dependent binding and phagocytosis of sheep red blood cells (SRBC). Oxysterols did not change both spontaneous and lipopolysaccharide-stimulated secretion of neopterin by PM. 25-OHCh dose-dependently and more efficiently than 7-KCh inhibited murine splenocyte secretion of MAF, which activity was determined by the ability of splenocyte-conditioned medium to stimulate ROI generation in PM. Both 25-OHCh and 7-KCh inhibited significantly proliferative activity of human mixed lymphocyte culture (MLC), as well as lymphocyte secretion of IaIF, which stimulates the expression of HLA antigens in cultured human monocytes. Purified Ch did not alter these parameters. These data showed, that some inflammatory functions of macrophages and lymphocytes may be modified by such environmental conditions as the presence of oxysterols.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1098-8823
DOI:	10.1016/S0090-6980(98)00024-0