Department of Biochemistry, Faculty of Pharmaceutical Sciences, Iwate Medical University, Futai Special Laboratory, Yahaba, Iwate 028-3694, Japan.
Biochem Biophys Res Commun. 2012 Aug 24;425(2):144-9. doi: 10.1016/j.bbrc.2012.07.050. Epub 2012 Jul 20.
Lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, induces strong proinflammatory responses, including the release of cytokines and nitric oxide from macrophage. In this study, we found that a murine macrophage-derived line, RAW264.7, became multinuclear through cell-cell fusion after incubation with highly purified LPS or synthetic lipid A in the presence of Ca(2+). The same cell line is known to differentiate into multinuclear osteoclast, which expresses a specific proton pumping ATPase together with osteoclast markers on stimulation by the extracellular domain of receptor activator of nuclear factor κB ligand (Toyomura, T., Murata, Y., Yamamoto, A., Oka, T., Sun-Wada, G.-H., Wada, Y. and Futai, M., 2003). The LPS-induced multinuclear cells did not express osteoclast-specific enzymes including tartrate-resistant acid phosphatase and cathepsin K. During multinuclear cell formation, the cells internalized more and larger polystyrene beads (diameter 6-15 μm) than mononuclear cells and osteoclasts. The internalized beads were located in lysosome-marker positive organelles, which were probably phagolysosomes. The LPS-induced multinuclear cell could be a good model system to study phagocytosis of large foreign bodies.
脂多糖（LPS）是革兰氏阴性细菌外膜的组成部分，可诱导强烈的促炎反应，包括细胞因子和一氧化氮从巨噬细胞释放。在这项研究中，我们发现，在用 Ca(2+)孵育高纯度 LPS 或合成脂质 A 后，源自鼠巨噬细胞系 RAW264.7 的细胞通过细胞-细胞融合变成多核。众所周知，同一种细胞系在受到核因子κB 配体受体激活剂（Toyomura，T.，Murata，Y.，Yamamoto，A.，Oka，T.，Sun-Wada，G.-H.，Wada，Y.和 Futai，M.，2003）细胞外结构域的刺激下，分化为多核破骨细胞，表达一种特定的质子泵 ATP 酶和破骨细胞标志物。LPS 诱导的多核细胞不表达破骨细胞特异性酶，包括抗酒石酸酸性磷酸酶和组织蛋白酶 K。在多核细胞形成过程中，细胞摄取的聚苯乙烯珠（直径 6-15 μm）比单核细胞和破骨细胞多且大。内化的珠子位于溶酶体标志物阳性细胞器中，可能是吞噬溶酶体。LPS 诱导的多核细胞可能是研究大异物吞噬的良好模型系统。
