A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor
01 May 1989-Journal of Experimental Medicine (Rockefeller University Press)-Vol. 169, Iss: 5, pp 1747-1756
TL;DR: It is suggested that the cell-killing activity of TNF is mediated by Fas antigen associated with the TNF-R, an mAb specific for a human cell surface component (termed anti-Fas mAb).
Abstract: We have prepared an mAb specific for a human cell surface component (termed anti-Fas mAb). Anti-Fas shows cell-killing activity that is indistinguishable from the cytolytic activity of TNF. Fas antigen was characterized by western blotting, indicating that Fas antigen is a cell surface protein with a molecular weight of 200,000, which is different from the molecular weight of TNF-R. Fas antigen, however, is co-downregulated with the TNF-R when cells sensitive to the cytolytic activity of TNF are incubated with either TNF or anti-Fas. In contrast, Fas antigen on cells insensitive to TNF is not co-downregulated with the TNF-R. We suggest that the cell-killing activity of TNF is mediated by Fas antigen associated with the TNF-R.
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TL;DR: This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan and by a Research Grant from the Princess Takamatsu Cancer Research Fund, and performed in part through Special Coordination Funds of the Science and Technology Agency of the Japanese Government.
5,054 citations
Cites background from "A cell-killing monoclonal antibody ..."
...Although both TNFR1 and TNFR2 canis well conserved (20–25...
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...Among members of this family, TRAF2 binds directly to TNFR2 and CD30 and indirectly to disorganized cell development in the brain (Kuida et al., 1996)....
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...To dissect the signal-transducing machinery for 1989; Yonehara et al., 1989; Itoh et al., 1991)....
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...On the other hand, TNFR2 (Yonehara et al., 1989; Itoh et al., 1991)....
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...(TNFR) family, which includes two TNFRs (TNFR1 and TNFR2), the receptor for lymphotoxin-b, the NGF recepDeath Factor and Receptor tor (p75), CD40, CD27, and CD30 (Nagata and Golstein, Fas Ligand and the TNF Family 1995)....
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TL;DR: Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells.
Abstract: Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Various cells express Fas, whereas FasL is expressed predominantly in activated T cells. In the immune system, Fas and FasL are involved in down-regulation of immune reactions as well as in T cell-mediated cytotoxicity. Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction.
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TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.
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TL;DR: A novel tumor necrosis factor (TNF) family member has been cloned and characterized, and the TRAIL gene is located on chromosome 3 at position 3q26, which is not close to any other known TNF ligand family members.
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TL;DR: The Ipr mice develop lymphadenopathy and suffer from a systemic lupus erythematosus-like autoimmune disease, indicating an important role for Fas antigen in the negative selection of autoreactive T cells in the thymus.
Abstract: Fas antigen is a cell-surface protein that mediates apoptosis. It is expressed in various tissues including the thymus and has structural homology with a number of cell-surface receptors, including tumour necrosis factor receptor and nerve growth factor receptor. Mice carrying the lymphoproliferation (lpr) mutation have defects in the Fas antigen gene. The lpr mice develop lymphadenopathy and suffer from a systemic lupus erythematosus-like autoimmune disease, indicating an important role for Fas antigen in the negative selection of autoreactive T cells in the thymus.
2,988 citations
References
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TL;DR: It is proposed that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.
Abstract: In studying "hemorrhagic necrosis" of tumors produced by endotoxin, it was found that the serum of bacillus Calmette--Guerin (BCG)-infected mice treated with endotoxin contains a substance (tumor necrosis factor; TNF) which mimics the tumor necrotic action of endotoxin itself. TNF-positive serum is as effective as endotoxin itself in causing necrosis of the sarcoma Meth A and other transplanted tumors. A variety of tests indicate that TNF is not residual endotoxin, but a factor released from host cells, probably macrophages, by endotoxin. Corynebacteria and Zymosan, which like BCG induce hyperplasia of the reticulo-endothelial system, can substitute for BCG in priming mice for release of TNF by endotoxin. TNF is toxic in vitro for two neoplastic cell lines; it is not toxic for mouse embryo cultures. We propose that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.
4,490 citations
2,505 citations
TL;DR: Recombinant tumour necrosis factor can be obtained by expression of its complementary DNA in Escherichia coli and induces the haemorrhagic necrosis of transplanted methylcholanthrene-induced sarcomas in syngeneic mice.
Abstract: Human tumour necrosis factor has about 30% homology in its amino acid sequence with lymphotoxin, a lymphokine that has similar biological properties. Recombinant tumour necrosis factor can be obtained by expression of its complementary DNA in Escherichia coli and induces the haemorrhagic necrosis of transplanted methylcholanthrene-induced sarcomas in syngeneic mice.
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TL;DR: The identity of cachectin and tumour necrosis factor has led to a new view of its therapeutic potential and its ability to induce wasting as well as a lethal state of shock.
Abstract: In response to invasive stimuli macrophages secrete cachectin, a multipotent protein. Prominent among its biological effects is the ability to induce wasting (cachexia) as well as a lethal state of shock. The identity of cachectin and tumour necrosis factor has led to a new view of its therapeutic potential.
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TL;DR: The observations indicate that the effects of rTNF-alpha on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo.
Abstract: Modulation of the growth of human and murine cell lines in vitro by recombinant human tumor necrosis factor-alpha (rTNF-alpha) and recombinant human interferon-gamma (rIFN-gamma) was investigated. rTNF-alpha had cytostatic or cytolytic effects on only some tumor cell lines. When administered together with rIFN-gamma, rTNF-alpha showed enhanced antiproliferative effects on a subset of the cell lines tested. In contrast to its effects on sensitive tumor cells, rTNF-alpha augmented the growth of normal diploid fibroblasts. Variations in the proliferative response induced by rTNF-alpha were apparently not due to differences in either the number of binding sites per cell or their affinity for rTNF-alpha. These observations indicate that the effects of rTNF-alpha on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo.
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