Effects of pravastatin on the in vitro phagocytic function and hydrogen peroxide production by monocytes of healthy individuals.
Macrophages play a part in pathogenesis of atherosclerosis, oxidizing LDL-cholesterol and transforming themselves in foam cells and producing free radicals of oxygen that may also oxidize LDL-cholesterol. HMG-CoA reductase inhibitors are very efficient in long-term control of atherogenesis acting by different mechanisms not fully established. Thus, we investigated the in vitro influence of pravastatin on phagocytosis and hydrogen peroxide production by monocytes of healthy individuals. Phagocytosis of Saccharomyces erevisiae by peripheral blood monocytes of 20 healthy individuals was assessed in the absence or presence of pravastatin. Hydrogen peroxide production was assessed based on the horseradish peroxidase-dependent oxidation of phenol red method. Pravastatin had no influence on phagocytosis through scavenger receptors, while it decreased by 20% the mean+/-SD phagocytic index of monocytes through complement receptors, from 141+/-77 to 113+/-56 (p=0.017), due to a decrease in the number of particles ingested by monocytes, from 2.1+/-0.5 to 1.7+/-0.3 (p=0.003). This statin also decreased the baseline production of hydrogen peroxide, by 7.7%, from 0.098+/-0.013 to 0.091+/-0.013 (OD by 2x10(5) monocytes per hour) (p=0.025). Pravastatin was able to decrease the phagocytosis through complement receptors and caused a decrease in the production of hydrogen peroxide by monocytes. It is possible this statin may directly inhibit the development of atherosclerotic plaque and its instability dependent on phagocytosis and the presence of reactive species of oxygen.
Muniz-Junqueira
Maria Imaculada
MI
Laboratory of Cellular Immunology, Faculty of Medicine, University of Brasilia, 70910-900 Brasilia, DF, Brazil. mimjunqueira@unb.br
Karnib
Silvana Ribeiro
SR
de Paula-Coelho
Viviany Nicolau
VN
Junqueira
Luiz Fernando
LF
D000328:Adult; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects*; D017035:Pravastatin / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000276:immunology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006861:Hydrogen Peroxide; D017035:Pravastatin