Takeda Yoshito, Tachibana Isao, Miyado Kenji, Kobayashi Masatoshi, Miyazaki Toru, Funakoshi Toshiki, Kimura Hiromi, Yamane Hiroyuki, Saito Yoshiyuki, Goto Hiroyuki, Yoneda Tsutomu, Yoshida Mitsuhiro, Kumagai Toru, Osaki Tadashi, Hayashi Seiji, Kawase Ichiro, Mekada Eisuke
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan.
J Cell Biol. 2003 Jun 9;161(5):945-56. doi: 10.1083/jcb.200212031.
Tetraspanins CD9 and CD81 facilitate the fusion between gametes, myoblasts, or virus-infected cells. Here, we investigated the role of these tetraspanins in the fusion of mononuclear phagocytes. Expression of CD9 and CD81 and their complex formation with integrins were up-regulated when blood monocytes were cultured under normal conditions. Under fusogenic conditions in the presence of Con A, CD9 and CD81 up-regulation was inhibited, and their complex formation with integrins was down-regulated. Anti-CD9 and -CD81 antibodies, which were previously shown to inhibit the fusion of gametes, myoblasts, and virus-infected cells, unexpectedly promoted the fusion of monocytes and alveolar macrophages. However, these effects were not due to altered cell adhesion, aggregation, or cytokine production. When stimulated in vitro or in vivo, alveolar macrophages and bone marrow cells of CD9- and CD81-null mice formed larger numbers of multinucleated cells than those of wild-type mice. Finally, CD9/CD81 double-null mice spontaneously developed multinucleated giant cells in the lung and showed enhanced osteoclastogenesis in the bone. These results suggest that CD9 and CD81 coordinately prevent the fusion of mononuclear phagocytes.
四跨膜蛋白CD9和CD81促进配子、成肌细胞或病毒感染细胞之间的融合。在此，我们研究了这些四跨膜蛋白在单核吞噬细胞融合中的作用。在正常条件下培养血液单核细胞时，CD9和CD81的表达及其与整合素的复合物形成上调。在伴刀豆球蛋白A存在的融合条件下，CD9和CD81的上调受到抑制，且它们与整合素的复合物形成下调。先前已证明抗CD9和抗CD81抗体可抑制配子、成肌细胞和病毒感染细胞的融合，但出乎意料的是，它们促进了单核细胞与肺泡巨噬细胞的融合。然而，这些作用并非由于细胞黏附、聚集或细胞因子产生的改变所致。在体外或体内受到刺激时，CD9和CD81基因敲除小鼠的肺泡巨噬细胞和骨髓细胞比野生型小鼠形成更多的多核细胞。最后，CD9/CD81双基因敲除小鼠的肺部自发形成多核巨细胞，且其骨骼中的破骨细胞生成增强。这些结果表明，CD9和CD81协同阻止单核吞噬细胞的融合。
