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Apoptosis‐inducing protein derived from hepatocyte selectively induces apoptosis in lymphocytes
Author(s) -
Ikeda Masanobu,
Yoshikawa Hideshi,
Liu Jie,
Nakajima Yasuo,
Akahane Yoshihiro,
Tasaka Kachio
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01542.x
Subject(s) - apoptosis , biology , immune system , microbiology and biotechnology , programmed cell death , hepatocyte , inhibitor of apoptosis , immunology , biochemistry , in vitro
Summary 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°) and acid (< pH 5) treatment but could not be neutralized by anti‐tumour necrosis factor‐α, anti‐Fas ligand, or anti‐transforming growth factor‐β 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.