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PMID: 12796480 Published · ppublish English Journal Article

Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes.

The Journal of cell biology ·Vol. 161 ·No. 5 ·2003-06-09 ·Pages 945-56

Takeda Y, Tachibana I, Miyado K, Kobayashi M, Miyazaki T, Funakoshi T, Kimura H, Yamane H, Saito Y, Goto H, Yoneda T, Yoshida M, Kumagai T, Osaki T, Hayashi S, Kawase I, Mekada E

Abstract

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.

MeSH Terms
Animals Antibodies/pharmacology Antigens, CD/genetics Bone Marrow Cells/cytology,drug effects,metabolism Cell Membrane/drug effects,metabolism Concanavalin A/pharmacology Down-Regulation/drug effects,physiology Humans Integrins/metabolism Leukocytes, Mononuclear/cytology,drug effects,metabolism Macrophages/cytology,drug effects,metabolism Membrane Fusion/drug effects,physiology Membrane Glycoproteins/antagonists & inhibitors,deficiency,genetics Membrane Proteins/antagonists & inhibitors,deficiency,genetics Mice Mice, Knockout Monocytes/cytology,drug effects,metabolism Osteoclasts/drug effects,metabolism Phagocytes/cytology,drug effects,metabolism Recombinant Fusion Proteins/pharmacology Tetraspanin 28 Tetraspanin 29 Up-Regulation/drug effects,physiology
Chemicals
Antibodies Antigens, CD CD81 protein, human CD9 protein, human Cd81 protein, mouse Cd9 protein, mouse Integrins Membrane Glycoproteins Membrane Proteins Recombinant Fusion Proteins Tetraspanin 28 Tetraspanin 29 Concanavalin A
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Takeda Yoshito
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan.
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
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200212031
Published
2003-06-09
Pages
945-56
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172976
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200212031 PMC Full Text View journal details
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