ABSTRACT
The presence of anti-polyethylene glycol (PEG) antibodies can limit the clinical efficacy of PEGylated drugs and cause anaphylactic reactions in patients. Monocytes/macrophages are effector cells involved in IgG-mediated passive systemic anaphylaxis. We studied the influence of human blood serum on the efficiency of uptake of PEGylated nanoparticles by human blood monocytes. It has been shown that magnetic nanoparticles modified with PEG-3000 and solid lipid nanoparticles containing PEG-2000 are avidly internalized by human blood monocytes in vitro, the uptake efficiency depends on the features (composition) of donor blood serum, but does not correlate with the level of the IgG antibody against PEG.
Subject(s)
Nanoparticles , Serum , Humans , Monocytes , Immunoglobulin G , Polyethylene GlycolsABSTRACT
In male Syrian hamsters fed a synthetic high-fat diet enriched with cholesterol (0.3%), administration of a polysaccharide from birch leaves L-rhamnopyranosyl-6-O-methyl-D-galacturonan (3 g/100 g of diet) resulted in a decrease in total cholesterol levels, mainly due to the LDL fraction, triglycerides, and bile acids in blood serum; the content of triglycerides and cholesterol in the liver also decreased, while excretion of bile acids with feces increased. Thus, the lipid-lowering effect of L-rhamnopyranosyl-6-O-methyl-D-galacturonan is related to its ability to bind bile acids in the intestine and interrupt their enterohepatic circulation.
Subject(s)
Betula , Cholesterol , Cricetinae , Male , Animals , Mesocricetus , Bile Acids and Salts/metabolism , Triglycerides , Pectins , Liver/metabolism , Diet, High-Fat , FecesABSTRACT
The in vitro addition of water-soluble polysaccharides isolated from the leaves of Crataegus sanguinea Pall. to culture of mouse peritoneal macrophages induced classical activation of antigen-presenting cells by increasing NO synthase activity and reducing arginase expression.
Subject(s)
Crataegus/chemistry , Macrophages, Peritoneal/drug effects , Nitric Oxide/metabolism , Polysaccharides/pharmacology , Animals , Arginase/drug effects , Arginase/metabolism , Cells, Cultured , Female , Macrophages, Peritoneal/enzymology , Macrophages, Peritoneal/metabolism , Mice , Mice, Inbred C57BL , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Polysaccharides/isolation & purification , Solubility , Water/chemistryABSTRACT
Addition of water-soluble polysaccharides isolated from Conium maculatum L. to the mouse peritoneal macrophage culture induces classical activation of antigen-presenting cells due to an increase in NO synthase activity and a decrease in arginase expression.
Subject(s)
Conium/metabolism , Polysaccharides/chemistry , Solubility , Water/chemistry , Alkaloids/metabolism , Animals , Antigen-Presenting Cells , Arginase/metabolism , Female , Immune System , Lymphocytes/metabolism , Mice , Mice, Inbred C57BL , Nitric Oxide/chemistry , PoaceaeABSTRACT
We studied activation of macrophages with humic acids extracted from peat of large deposits in the Tomsk region by two extraction methods: by hydroxide or sodium pyrophosphate. Humic acid of lowland peat types containing large amounts of aromatic carbon, phenolic and alcohol groups, carbohydrate residues and ethers, irrespectively of the extraction methods contained LPS admixture that probably determines their activating properties. Humic acid of upland peat types characterized by high content of carbonyl, carboxyl, and ester groups enhance NO production and reduce arginase expression, but these effects were minimized when sodium hydroxide was used as an extraction solvent. Pyrophosphate samples of the upland peat types were characterized by aromaticity and diversity of functional groups and have a significant advantage because of they induce specific endotoxin-independent stimulating action on antigen presenting cells.
Subject(s)
Complex Mixtures/pharmacology , Humic Substances/analysis , Macrophages, Peritoneal/drug effects , Soil/chemistry , Animals , Arginase/metabolism , Carbon/analysis , Complex Mixtures/isolation & purification , Diphosphates/analysis , Diphosphates/chemistry , Female , Lipopolysaccharides/pharmacology , Liquid-Liquid Extraction/methods , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/immunology , Male , Mice , Mice, Inbred C57BL , Nitric Oxide/biosynthesis , Phenols/analysis , Polymyxin B/pharmacology , Primary Cell Culture , Sodium Hydroxide/chemistryABSTRACT
A screening study of biological activity of native humic acids isolated from peat was performed; several physical and chemical parameters of their structures were studied by UV- and infrared spectroscopy. Spectroscopy yielded similar shape of light absorption curves of humic acids of different origin, which can reflect similarity of general structural principles of these substances. Alkaline humic acids have more developed system of polyconjugation, while molecular structures of pyrophosphate humic acids were characterized by higher aromaticity and condensation indexes. Biological activity of the studied humic acids was assessed by NO-stimulating capacity during their culturing with murine peritoneal macrophages in a wide concentration range. It was shown that due to dose-dependent enhancement of NO production humic acids can change the functional state of macrophages towards development of pro-inflammatory properties. These changes were associated with high activity of humic acids isolated by pyrophosphate extraction, which allows considering effects of isolation method on biological activity.
Subject(s)
Humic Substances , Macrophages, Peritoneal/metabolism , Nitric Oxide/biosynthesis , Soil/chemistry , Animals , Cells, Cultured , Drug Evaluation, Preclinical , Female , Macrophages, Peritoneal/drug effects , Male , Mice, Inbred C57BLABSTRACT
Screening study of the effects of sweet flag (Acorus calamus L.) rhizome and clover (Trifolium pratense L.) aerial part on the production of NO by mouse macrophages was carried out. The polysaccharides were separated by ion exchange chromatography into fractions differing by monomeric composition and ramification type and were used in concentrations of 20, 40, and 100 µg/ml. Four fractions of Acorus calamus L. (PSF-101, PSF-102, PSF-103, and PSF-105), used in different concentrations, moderately stimulated nitrite production by macrophages. Three of five Trifolium pratense L. polysaccharides (PS62-3, PS62-4, and PS62-5) exhibited a significant specific effect on NO production. Rhamnogalactouronans from clover PS63-3 in all concentrations and from PS62-5 in a concentration of 100 µg/ml exhibited the highest activity, comparable to the NO-stimulatory activity of the reference LPS, while polysaccharide PS62-3 in a concentration of 40 µg/ml exhibited even higher activity.
