Stossel T P, Mason R J, Smith A L
J Clin Invest. 1974 Sep;54(3):638-45. doi: 10.1172/JCI107801.
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.
通过在泛影葡胺 - 菲可梯度上沉降从正常人外周血中获得的富含人血单核细胞的细胞悬液，或从中性粒细胞减少和单核细胞增多患者的血液中获得的细胞悬液，在与聚苯乙烯珠或热灭活的表皮葡萄球菌孵育期间积累了丙二醛，这是脂质过氧化的一种不稳定分解代谢产物。主要由粒细胞组成或通过密度梯度沉降纯化的混合血白细胞在与这些颗粒孵育期间不积累丙二醛，但在摄取含亚麻酸的颗粒时会积累。比较了来自相同供体的单核细胞富集制剂和纯化粒细胞制剂的磷脂脂肪酸组成。富含单核细胞的制剂中磷脂中花生四烯酸（20:4）的摩尔分数比纯化的粒细胞高62%。这些发现表明，人类单核细胞可能由于其膜中多不饱和脂肪酸含量较高，在内吞过程中比粒细胞过氧化更多的内源性脂质。正常人粒细胞有过氧化摄取脂质的能力。然而，两名慢性肉芽肿病患者的混合白细胞在吞噬含亚麻酸的颗粒时产生的丙二醛很少。因此，脂质过氧化能力与细胞氧代谢有关，慢性肉芽肿病粒细胞在这一功能上存在缺陷。通过四甲氧基丙烷水解、从过氧化亚麻酸中提取或从吞噬兔肺泡巨噬细胞提取物中纯化化学制备的丙二醛对大肠杆菌和表皮葡萄球菌有杀菌活性。因此，脂质氢过氧化物的有毒分解代谢产物可能增强单核吞噬细胞中过氧化氢的杀菌活性。
