Suppression of FRP-1/CD98-mediated multinucleated giant cell and osteoclast formation by an anti-FRP-1/CD98 mAb, HBJ 127, that inhibits c-src expression.
When anti-CD98 mAb 6-1-13, 4-5-1, or 38-2-2 was added to the culture fluids of monocytes, extensive cell aggregation and polykaryocyte formation were induced. These multinucleated giant cells were tartrate-resistant acid phosphatase (TRAP) positive. On the other hand, when monocytes were incubated with another anti-CD98 mAb, HBJ 127, polykaryocyte formation was not detected, although extensive cell aggregation was induced. When HBJ 127 and 6-1-13 were simultaneously added to the culture fluids, anti-CD98 mAb-induced cell fusion was inhibited almost completely. HBJ 127 suppressed formation of 6-1-13-induced cell fusion in a dose-dependent manner. If, however, HBJ 127 was added after incubation of monocytes with mAb 6-1-13 for 6 h, an appreciable degree of TRAP-positive polykaryocyte formation was found. The bindings of 6-1-13 and HBJ 127 were not mutually competed. When monocytes were incubated with 6-1-13 or HBJ 127, 6-1-13 induced c-src mRNA, while HBJ 127 did not. Furthermore, when monocytes were incubated with both 6-1-13 and HBJ 127, c-src mRNA could not be detected, showing that HBJ 127 suppresses c-src expression. Therefore, CD98-mediated osteoclast formation can be regulated by modification of CD98 system.
Tajima
M
M
Department of Microbiology, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514, Japan.
Higuchi
S
S
Higuchi
Y
Y
Miyamoto
N
N
Uchida
A
A
Ito
M
M
Nishio
M
M
Komada
H
H
Kawano
M
M
Kusagawa
S
S
Tsurudome
M
M
Ito
Y
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D027261:Fusion Regulatory Protein-1; D005786:Gene Expression Regulation; D015726:Giant Cells / Q000166:cytology*; D006801:Humans; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D016392:Proto-Oncogene Proteins pp60(c-src)