van Rooijen Nico, Hendrikx Esther
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Methods Mol Biol. 2010;605:189-203. doi: 10.1007/978-1-60327-360-2_13.
A liposome mediated macrophage "suicide" approach has been developed, based on the liposome mediated internalization of the small hydrophilic molecule clodronate in macrophages J Leukoc Biol 62:702, 1997. This molecule has a very short half life when released in the circulation, but does not easily cross phospholipid bilayers of liposomes or cell membranes. As a consequence, once ingested by a macrophage in a liposome encapsulated form, it will be accumulated within the cell as soon as the liposomes are digested with the help of its lysosomal phospholipases. At a certain intracellular clodronate concentration, the macrophage is eliminated by apoptosis. Given the fact that, neither the liposomal phospholipids chosen, nor clodronate are toxic to other (non-phagocytic) cells, this method has proven its efficacy and specificity for depletion of macrophage subsets in various organs. In several cases, organ specific depletion can be obtained by choosing the right administration route for the clodronate liposomes.
基于脂质体介导的小亲水分子氯膦酸盐在巨噬细胞中的内化作用，已经开发出一种脂质体介导的巨噬细胞“自杀”方法（《白细胞生物学杂志》62:702，1997年）。该分子在循环中释放时半衰期很短，但不容易穿过脂质体或细胞膜的磷脂双层。因此，一旦巨噬细胞以脂质体包裹的形式摄取该分子，在溶酶体磷脂酶的帮助下，脂质体被消化后，它就会在细胞内积累。当细胞内氯膦酸盐达到一定浓度时，巨噬细胞会通过凋亡被清除。鉴于所选择的脂质体磷脂和氯膦酸盐对其他（非吞噬）细胞均无毒性，该方法已证明其在耗尽各种器官中巨噬细胞亚群方面的有效性和特异性。在几种情况下，通过为氯膦酸盐脂质体选择正确的给药途径，可以实现器官特异性耗尽。
