A new apoptotic pathway for the complement factor B-derived fragment Bb.
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.
Uwai
M
M
Department of Hematology, Jichi Medical School, Kawachi, Tochigi, Japan.
Terui
Y
Y
Mishima
Y
Y
Tomizuka
H
H
Ikeda
M
M
Itoh
T
T
Mori
M
M
Ueda
M
M
Inoue
R
R
Yamada
M
M
Hayasawa
H
H
Horiuchi
T
T
Niho
Y
Y
Matsumoto
M
M
Ishizaka
Y
Y
Ikeda
K
K
Ozawa
K
K
Hatake
K
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D003176:Complement C3 / Q000494:pharmacology; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000235:genetics / Q000378:metabolism; D007938:Leukemia / Q000473:pathology / Q000503:physiopathology; D008223:Lymphoma / Q000473:pathology / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000502:physiology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011951:Receptors, Complement / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D000911:Antibodies, Monoclonal; D003176:Complement C3; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016167:Integrin alphaXbeta2; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D011951:Receptors, Complement; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D015240:Phorbol 12,13-Dibutyrate; D003179:Complement C3b; D051561:Complement C3 Convertase, Alternative Pathway