van Rooijen N, Sanders A
Department of Cell Biology & Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
J Leukoc Biol. 1997 Dec;62(6):702-9. doi: 10.1002/jlb.62.6.702.
In mammals, macrophages are multifunctional cells. Apart from their scavenger role in the clearance of non-self materials such as microorganisms and altered-self materials such as apoptotic cells, senescent erythrocytes, immune complexes, and inflammatory products, they play a crucial role in the regulation of both innate and acquired immunity. Whereas the former activity is based on phagocytosis and intracellular degradation, the latter activity largely depends on the production and secretion of a panel of regulatory molecules such as cytokines, chemokines, and nitrogen oxide (NO). Depletion of macrophages and blocking of phagocytosis form important approaches to study the role of these cells in various host defense mechanisms. Moreover, the efficacy of drug- and gene-targeting, based on the application of particulate carrier devices, can be improved in this way. However, compounds originally described as efficacious blockers of phagocytosis simultaneously activate their production of cytokines and NO. Moreover, elimination, blocking, as well as activation of macrophages are all dependent on the concentration of such compounds. When administered in vivo, they will reach some macrophages in a high and others in a low concentration. As a consequence, the former cells may be eliminated or blocked, whereas the latter are activated by the same treatment. In this review, the various methods for suppression of macrophage functions are compared and requirements for the development of new, selective, and organ-specific macrophage-suppressing devices are discussed.
在哺乳动物中，巨噬细胞是多功能细胞。除了在清除非自身物质（如微生物）和改变自身物质（如凋亡细胞、衰老红细胞、免疫复合物和炎症产物）方面发挥清除作用外，它们在先天免疫和获得性免疫的调节中也起着关键作用。前者的活动基于吞噬作用和细胞内降解，而后者的活动很大程度上依赖于一系列调节分子的产生和分泌，如细胞因子、趋化因子和一氧化氮（NO）。巨噬细胞的耗竭和吞噬作用的阻断是研究这些细胞在各种宿主防御机制中作用的重要方法。此外，基于颗粒载体装置的药物靶向和基因靶向的疗效也可以通过这种方式得到提高。然而，最初被描述为吞噬作用有效阻断剂的化合物同时会激活它们产生细胞因子和NO。此外，巨噬细胞的消除、阻断以及激活都取决于此类化合物的浓度。当在体内给药时，它们会以高浓度到达一些巨噬细胞，而以低浓度到达另一些巨噬细胞。因此，前者的细胞可能会被消除或阻断，而后者则会被相同的处理激活。在这篇综述中，比较了抑制巨噬细胞功能的各种方法，并讨论了开发新型、选择性和器官特异性巨噬细胞抑制装置的要求。
