Lipid Peroxidation by Human Blood Phagocytes

摘要

Cell suspensions enriched in human blood monocytes, obtained from normal peripheral blood by sedimentation on sodium diatrizoate-Ficoll gradients or from the blood of patients with neutropenia and monocytosis, accumulated malonyldialdehyde, a labile catabolite of lipid peroxidation, during incubations with polystyrene beads or heat-killed Staphylococcus epidermidis. Mixed blood leukocytes principally composed of granulocytes or granulocytes purified by density gradient sedimentation did not accumulate malonyldialdehyde during incubations with these particles, but did when ingesting particles containing linolenate. The phospholipid fatty acid composition of monocyte-enriched and purified granulocyte preparations from the same donors were compared. The molar fraction of arachidonate (20:4) in phospholipids from monocyte-rich preparations was 62% greater than that of purified granulocytes. The findings indicate that human monocytes, possibly because of a greater content of polyunsaturated fatty acids in their membranes, peroxidize a greater quantity of endogenous lipids than granulocytes during endocytosis. Normal human granulocytes have the capacity to peroxidize ingested lipids. However, mixed leukocytes from two patients with chronic granulomatous disease produced little malonyldialdehyde when engulfing linolenate-containing particles. Therefore the capacity to peroxidize lipid is related to cellular oxygen metabolism, a function in which chronic granulomatous disease granulocytes are dificient.Malonyldialdehyde chemically prepared by hydrolysis of tetramethoxypropane, by extraction from peroxidized linolenic acid, or purified from extracts of phagocytizing rabbit alveolar macrophages had bactericidal activity against Escherichia coli and S. epidermidis. Therefore, toxic catabolites of lipid hydroperoxides may potentiate the bactericidal activity of hydrogen peroxide in mononuclear phagocytes.