Effects of microparticle size and Fc density on macrophage phagocytosis.

Effects of microparticle size and Fc density on macrophage phagocytosis.
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微粒子大小和 Fc 密度对巨噬细胞吞噬作用的影响

DOI:
10.1371/journal.pone.0060989
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Sulchek T
Sulchek T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pacheco P;White D;Sulchek T

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巨噬细胞中吞噬作用的受控诱导提供了治疗性调节免疫系统以及改善用于免疫处理的化学品或生物制剂的递送的能力。通过Fc受体介导的吞噬作用使巨噬细胞的颗粒摄取最大化可能导致药物或疫苗开发中的新递送机制。独立地和组合地检查Fc配体密度和粒度,以优化和调节调理的微粒的吞噬作用。我们发现小聚苯乙烯颗粒(0.5 μm至2 μm)的内化效率受到Fc配体密度变化的显著影响,而大于2 μm的颗粒在内化和Fc密度之间几乎没有相关性。我们发现,虽然巨噬细胞可以有效地吞噬大量的较小的颗粒,吞噬的颗粒的总体积是通过非特异性摄取较大的微粒最大化。因此,较大的微粒可能更有效地向巨噬细胞提供更大的治疗有效载荷,但较小的调理微粒可以向更大比例的巨噬细胞群体提供生物活性物质。本研究首次将启动巨噬细胞吞噬作用的Fc密度和微粒大小的物理和生物学性质作为自变量处理。定义影响吞噬效率的物理和生物学参数将导致微粒递送到巨噬细胞的改进方法。
Controlled induction of phagocytosis in macrophages offers the ability to therapeutically regulate the immune system as well as improve delivery of chemicals or biologicals for immune processing. Maximizing particle uptake by macrophages through Fc receptor-mediated phagocytosis could lead to new delivery mechanisms in drug or vaccine development. Fc ligand density and particle size were examined independently and in combination in order to optimize and tune the phagocytosis of opsonized microparticles. We show the internalization efficiency of small polystyrene particles (0.5 µm to 2 µm) is significantly affected by changes in Fc ligand density, while particles greater than 2 µm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population. This study is the first to treat as independent variables the physical and biological properties of Fc density and microparticle size that initiate macrophage phagocytosis. Defining the physical and biological parameters that affect phagocytosis efficiency will lead to improved methods of microparticle delivery to macrophages.
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