Characterization of murine TWEAK and its receptor (Fn14) by monoclonal antibodies.
In the present study, we characterized murine TWEAK and its receptor (Fn14) by generating cDNA transfectants and specific monoclonal antibodies (mAbs). Recombinant murine TWEAK bound to murine Fn14-transfected L5178Y (mFn14/L5178Y) cells and induced cell death. Some anti-human Fn14 mAbs we previously generated strongly cross-reacted with murine Fn14 and induced cell death in mFn14/L5178Y cells. Murine TWEAK-transfected L5178Y cells expressed murine TWEAK on cell surface and secreted functional TWEAK, which were detected by a newly generated anti-murine TWEAK mAb (MTW-1). Although thioglycolate-elicited murine peritoneal macrophages did not express a detectable level of TWEAK on their surface, they secreted functional TWEAK that was cytotoxic against mFn14/L5178Y cells and neutralized by MTW-1. The anti-murine TWEAK and Fn14 mAbs will be useful for further investigating the physiological and pathological functions of TWEAK and Fn14.
Nakayama
Masafumi
M
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Harada
Norihiro
N
Okumura
Ko
K
Yagita
Hideo
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology; D002460:Cell Line; D000074049:Cytokine TWEAK; D018076:DNA, Complementary / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074050:TWEAK Receptor; D014162:Transfection; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D000074049:Cytokine TWEAK; D018076:DNA, Complementary; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; C491645:Tnfsf12 protein, mouse; D048069:Tumor Necrosis Factors