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.
Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes
Abbreviations used in this paper: 1α,25(OH)2D3, 1α,25-dihydroxyvitamin D3; BAL, bronchoalveolar lavage; MGC, multinucleated giant cell; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; sRANKL, soluble RANKL; TRAP, tartrate-resistant acid phosphatase.
Yoshito Takeda, Isao Tachibana, Kenji Miyado, Masatoshi Kobayashi, Toru Miyazaki, Toshiki Funakoshi, Hiromi Kimura, Hiroyuki Yamane, Yoshiyuki Saito, Hiroyuki Goto, Tsutomu Yoneda, Mitsuhiro Yoshida, Toru Kumagai, Tadashi Osaki, Seiji Hayashi, Ichiro Kawase, Eisuke Mekada; Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes . J Cell Biol 9 June 2003; 161 (5): 945–956. doi: https://doi.org/10.1083/jcb.200212031
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