Huong T M, Harashima H, Kiwada H
Faculty of Pharmaceutical Sciences, The University of Tokushima, Japan.
Biol Pharm Bull. 1998 Sep;21(9):969-73. doi: 10.1248/bpb.21.969.
The uptake mechanisms of liposomes by rat peritoneal macrophages (PMs) were investigated. Incubation of liposomes with fresh rat serum enhanced the uptake of liposomes depending on the liposome size and cholesterol (CH) content. The binding of liposomes was also enhanced by serum, and this increase depended on the size and CH content as in the case of liposome uptake, which suggested that the binding of opsonized liposomes with PMs govern the extent in liposome uptake. The rate constant for the internalization (k(int)) was calculated by measuring both uptake and binding. The k(int) cannot explain the variation of liposome uptake for different sizes and CH contents. The kint values for liposomes with high (44%) and medium (33%) CH contents were constant (2.5 h(-1)) , while those for liposomes with low (22%) CH content were significantly elevated (5-9 h(-1)). These results indicate the presence of at least two kinds of uptake mechanisms of liposomes. Treatment of serum with anti-C3 antibody completely inhibited the enhanced uptake of CH-high, large liposomes, which suggested that complement receptor-mediated phagocytosis may be an uptake mechanism for CH-high and -medium liposomes. In addition, complement-independent enhanced uptake was suggested for CH-low liposomes, since no inhibition was observed for CH-low liposomes by anti-C3 antibody and these liposomes were disintegrated in serum via complement-independent pathway. These results provided evidence that PMs take up liposomes via complement-dependent and independent mechanisms depending on the CH content of the liposomes.
研究了大鼠腹膜巨噬细胞（PMs）对脂质体的摄取机制。脂质体与新鲜大鼠血清孵育可增强脂质体的摄取，这取决于脂质体大小和胆固醇（CH）含量。血清也增强了脂质体的结合，这种增加如同脂质体摄取情况一样取决于大小和CH含量，这表明调理素化脂质体与PMs的结合决定了脂质体摄取的程度。通过测量摄取和结合来计算内化速率常数（k(int)）。k(int)无法解释不同大小和CH含量的脂质体摄取变化。高CH含量（44%）和中等CH含量（33%）的脂质体的kint值恒定（2.5 h(-1)），而低CH含量（22%）的脂质体的kint值显著升高（5 - 9 h(-1)）。这些结果表明脂质体至少存在两种摄取机制。用抗C3抗体处理血清可完全抑制高CH含量、大脂质体摄取的增强，这表明补体受体介导的吞噬作用可能是高CH含量和中等CH含量脂质体的摄取机制。此外，对于低CH含量脂质体，提示存在不依赖补体的增强摄取，因为抗C3抗体对低CH含量脂质体未观察到抑制作用，且这些脂质体在血清中通过不依赖补体的途径解体。这些结果提供了证据，表明PMs根据脂质体的CH含量通过依赖补体和不依赖补体的机制摄取脂质体。
