Moghimi S M, Patel H M
Department of Biochemistry, Charing Cross and Westminster Medical School, London, UK.
Biochim Biophys Acta. 1992 Jun 29;1135(3):269-74. doi: 10.1016/0167-4889(92)90230-9.
We investigated the opsonic effect of serum on the phagocytosis of cholesterol-poor and cholesterol-rich liposomes with freshly prepared rat bone marrow and peritoneal phagocytes in suspension. The presence of serum in incubation increased the uptake of cholesterol-rich but not cholesterol-poor liposomes in bone marrow cells, whereas serum enhances phagocytosis of both liposome preparations in peritoneal phagocytes. The opsonic activity of serum on the uptake of liposomes by both cell types is destroyed by heat, ammonium hydroxide, and zymosan treatments of serum, which suggests the involvement of complement in phagocytosis of liposomes. However, bone marrow cells and peritoneal macrophages responded differently when incubated with dialysed or EGTA-chelated serum. These treatments result in complete loss of the opsonic effect of serum on the uptake of liposome in bone marrow cells. Addition of serum dialysate or divalent cations to dialysed serum do not reinstall its lost opsonic activity. Thus these results shade doubt on possibility of involvement of complements in phagocytosis of liposomes by bone marrow cells. Dialysed or EGTA-treated serum also failed to promote liposome uptake by peritoneal macrophages but unlike in the case of bone marrow cells replacement of divalent cations to such sera reinstalls its opsonic activity and enhances phagocytosis of liposomes by peritoneal macrophages. These observations suggest the involvement of different serum components on liposome uptake by bone marrow cells and peritoneal macrophages, and emphasize the complexities associated with RES-mediated blood clearance of the intravenously injected liposomes. The properties of these opsonins are compared with those of 'liver-' and 'spleen-specific' opsonins responsible for phagocytosis of liposomes by Kupffer cells and spleen macrophages, respectively [4]. It is suggested that these tissue specific opsonins are responsible for distribution of intravenously injected liposomes in various organs of the reticuloendothelial system.
我们用新鲜制备的大鼠骨髓和腹腔吞噬细胞悬浮液,研究了血清对低胆固醇和高胆固醇脂质体吞噬作用的调理效应。孵育体系中存在血清时,骨髓细胞对高胆固醇脂质体的摄取增加,但对低胆固醇脂质体的摄取无影响;而血清增强了腹腔吞噬细胞对两种脂质体制剂的吞噬作用。血清对两种细胞类型摄取脂质体的调理活性,会因血清经加热、氢氧化铵和酵母聚糖处理而被破坏,这表明补体参与了脂质体的吞噬过程。然而,当用透析或EGTA螯合的血清孵育时,骨髓细胞和腹腔巨噬细胞的反应不同。这些处理导致血清对骨髓细胞摄取脂质体的调理效应完全丧失。向透析血清中添加血清透析液或二价阳离子,并不能恢复其丧失的调理活性。因此,这些结果对补体参与骨髓细胞吞噬脂质体的可能性提出了质疑。透析或经EGTA处理的血清也不能促进腹腔巨噬细胞摄取脂质体,但与骨髓细胞不同的是,向这类血清中补充二价阳离子可恢复其调理活性,并增强腹腔巨噬细胞对脂质体的吞噬作用。这些观察结果表明,不同的血清成分参与了骨髓细胞和腹腔巨噬细胞对脂质体的摄取,并强调了与网状内皮系统介导的静脉注射脂质体血液清除相关的复杂性。将这些调理素的特性与分别负责枯否细胞和脾巨噬细胞吞噬脂质体的“肝脏特异性”和“脾脏特异性”调理素的特性进行了比较[4]。有人提出,这些组织特异性调理素负责静脉注射脂质体在网状内皮系统各器官中的分布。