Document Detail


A humanized anti-human Fas antibody, R-125224, induces apoptosis in type I activated lymphocytes but not in type II cells.
MedLine Citation:
PMID:  16361317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fas-mediated apoptosis plays an important role in the immune system, including the elimination of autoreactive lymphoid cells. The Fas-mediated signaling pathway is classified into two types, type I and type II, in human lymphoid cell lines. We investigated whether a humanized anti-human Fas mAb, R-125224, has cell selectivity in induction of apoptosis. R-125224 induced apoptosis in H9 cells, SKW6.4 cells and activated human lymphocytes when cross-linked with anti-human IgG. On the other hand, R-125224 did not induce apoptosis in HPB-ALL cells, Jurkat cells or human hepatocytes. By analysis of death-inducing signaling complex formation, it was demonstrated that R-125224 induced apoptosis selectively in type I cells but not in type II cells. Type I cells also expressed more Fas and had more Fas-clustering activity than type II cells. Moreover, co-localization of these clusters and GM1, which is an sphingoglycolipid associated with lipid rafts, was detected. It was also shown that R-125224 treatment could reduce the number of activated human CD3+Fas+ cells in a SCID mouse model in vivo. Thus, we demonstrated that R-125224 induces apoptosis specifically in type I cells in vitro and in vivo.
Authors:
Junichi Nakayama; Yukie Ogawa; Yasushi Yoshigae; Yoshiko Onozawa; Akiko Yonemura; Motoko Saito; Kimihisa Ichikawa; Takashi Yamoto; Tomoaki Komai; Toru Tatsuta; Masahiko Ohtsuki
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Publication Detail:
Type:  Journal Article     Date:  2005-12-16
Journal Detail:
Title:  International immunology     Volume:  18     ISSN:  0953-8178     ISO Abbreviation:  Int. Immunol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-27     Completed Date:  2006-07-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8916182     Medline TA:  Int Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  113-24     Citation Subset:  IM    
Affiliation:
Biological Research Laboratories, Sankyo Co., Ltd, Tokyo 140-8710, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology,  pharmacology*
Antigens, CD3 / immunology
Antigens, CD95 / immunology*
Apoptosis / drug effects*,  immunology
Hepatocytes / immunology
Humans
Immunologic Capping / drug effects,  immunology
Jurkat Cells
Lymphocyte Activation / drug effects*,  immunology
Mice
Mice, SCID
Signal Transduction / drug effects,  immunology
Th1 Cells / immunology*
Th2 Cells / immunology*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD3; 0/Antigens, CD95

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