Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes.
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.
Takeda
Yoshito
Y
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan.
Tachibana
Isao
I
Miyado
Kenji
K
Kobayashi
Masatoshi
M
Miyazaki
Toru
T
Funakoshi
Toshiki
T
Kimura
Hiromi
H
Yamane
Hiroyuki
H
Saito
Yoshiyuki
Y
Goto
Hiroyuki
H
Yoneda
Tsutomu
T
Yoshida
Mitsuhiro
M
Kumagai
Toru
T
Osaki
Tadashi
T
Hayashi
Seiji
S
Kawase
Ichiro
I
Mekada
Eisuke
E
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D015703:Antigens, CD; C554798:CD81 protein, human; C554869:CD9 protein, human; C554799:Cd81 protein, mouse; C554870:Cd9 protein, mouse; D016023:Integrins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D003208:Concanavalin A