1. A new apoptotic pathway for the complement factor B-derived fragment Bb.
- Author
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Uwai M, Terui Y, Mishima Y, Tomizuka H, Ikeda M, Itoh T, Mori M, Ueda M, Inoue R, Yamada M, Hayasawa H, Horiuchi T, Niho Y, Matsumoto M, Ishizaka Y, Ikeda K, Ozawa K, and Hatake K
- Subjects
- Antibodies, Monoclonal pharmacology, Apoptosis drug effects, Blotting, Western, Complement C3 pharmacology, Complement C3 Convertase, Alternative Pathway, Complement C3b immunology, Complement C3b pharmacology, Dose-Response Relationship, Drug, Fas Ligand Protein, Gene Expression drug effects, HL-60 Cells, Humans, Integrin alphaXbeta2 genetics, Integrin alphaXbeta2 metabolism, Leukemia pathology, Leukemia physiopathology, Lymphoma pathology, Lymphoma physiopathology, Membrane Glycoproteins physiology, Peptide Fragments immunology, Peptide Fragments pharmacology, Phorbol 12,13-Dibutyrate pharmacology, RNA, Messenger metabolism, Receptors, Complement physiology, Receptors, Tumor Necrosis Factor physiology, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha physiology, fas Receptor physiology, Apoptosis physiology, Complement C3b physiology, Peptide Fragments physiology
- Abstract
Apoptosis is involved in both the cellular and humoral immune system destroying tumors. An apoptosis-inducing factor from HL-60 myeloid leukemia cells was obtained, purified, and sequenced. The protein found has been identified as a human complement factor B-derived fragment Bb, although it is known that factor B is able to induce apoptosis in several leukemia cell lines. Monoclonal antibodies against fragment Ba and Bb inhibited the apoptotic activity of factor B. When the purified fragment Bb was used for apoptosis induction, only the anti-Bb antibody inhibited Bb-induced apoptosis, and not the anti-Ba antibody. The apoptosis-inducing activity was found to be enhanced under conditions facilitating the formation of Bb. Blocking TNF/TNFR or FasL/Fas interactions did not interfere with the factor B-induced apoptosis. CD11c (iC3bR) acts as the main subunit of a heterodimer binding to fragment Bb in the apoptosis pathway, and the factor B-derived fragment Bb was found to possess the previously unknown function of inducing apoptosis in leukemic cells through a suicide mechanism of myeloid lineage cells during the differentiation stage., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
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