Apoptosis-inducing protein derived from hepatocyte selectively induces apoptosis in lymphocytes.
The liver is where lymphocytes undergo activation-induced cell death (AICD) at the resolution phase of an immune response, which is crucial for homeostasis of the immune system and prevention of autoimmunity. Exploring the machinery of AICD in the liver, we found that a primary culture supernatant of murine hepatocytes had an antiproliferative effect on antigen-stimulated T clone and T lymphoma cells. Biological study showed that the antiproliferation was due to induction of apoptosis in a caspase-dependent manner. The apoptosis-inducing potential was sensitive to trypsin, heat (> 70 degrees ) and acid (< pH 5) treatment but could not be neutralized by anti-tumour necrosis factor-alpha, anti-Fas ligand, or anti-transforming growth factor-beta antibodies. Biochemical study of the isolated and purified apoptosis-inducing component from the supernatant showed that it was a protein with a molecular mass of about 68,000-70,000. It induced apoptotic change in murine T and B cells, and to a lesser degree, in human lymphoid cells, but not in macrophages. Biochemical and biological characteristics distinguish this protein from others that have been reported to induce apoptosis of lymphocytes. The identification of an apoptosis-inducing protein derived from murine hepatocytes, which selectively induces apoptosis in lymphocytes, suggests one possible mechanism for immune suppression in the liver.
Ikeda
Masanobu
M
First Department of Internal Medicine, Yamanashi Medical University, Tamaho, Yamanashi, Japan.
Yoshikawa
Hideshi
H
Liu
Jie
J
Nakajima
Yasuo
Y
Akahane
Yoshihiro
Y
Tasaka
Kachio
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D051033:Apoptosis Inducing Factor; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D053938:DNA Fragmentation; D005260:Female; D005420:Flavoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D017077:Culture Media, Conditioned; D005420:Flavoproteins; D008565:Membrane Proteins; C494830:AIFM1 protein, mouse