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PMID: 3487788 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Tumor necrosis factor: a potent effector molecule for tumor cell killing by activated macrophages.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 14 ·1986-07-00 ·Pages 5233-7

Urban JL, Shepard HM, Rothstein JL, Sugarman BJ, Schreiber H

Abstract

Activated macrophages (aM phi) destroy more effectively cancer cells than normal cells. The mechanism by which macrophages destroy cancer cells is not known. We report here that tumor cells susceptible to aM phi were killed by recombinant (r) tumor necrosis factor type alpha (TNF-alpha), whereas variant tumor cells resistant to aM phi after selection in vitro or in vivo were resistant to killing by rTNF-alpha. The converse selection for rTNF-alpha-resistant variants resulted in cells that were also resistant to killing by aM phi. The sensitivity of macrophage-resistant variants was not changed to other tumoricidal cells or soluble mediators, except that the macrophage-resistant variants were also resistant to the effects of another cytotoxic protein, B-cell lymphotoxin, which is structurally related to rTNF-alpha. Similar results were obtained regardless of whether short-term or long-term cytotoxic effects of aM phi were measured. Finally, it was shown that killing of tumor cells by murine aM phi was completely inhibited with a polyclonal antibody that neutralizes the effects of murine TNF-alpha. These results suggest a major role for TNF-alpha in tumor cell destruction by aM phi in vitro and in vivo.

MeSH Terms
Animals Cytotoxicity, Immunologic/drug effects Drug Resistance Glycoproteins/pharmacology,therapeutic use Humans Lymphotoxin-alpha/pharmacology Macrophage Activation Mice Mice, Inbred C3H Neoplasms, Experimental/drug therapy Recombinant Proteins/pharmacology Tumor Necrosis Factor-alpha
Chemicals
Glycoproteins Lymphotoxin-alpha Recombinant Proteins Tumor Necrosis Factor-alpha
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Urban J L
Shepard H M
Rothstein J L
Sugarman B J
Schreiber H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.14.5233
Published
1986-07-00
Pages
5233-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323925
Subset
IM
Grants
NCI NIH HHS · CA-19266 · United States
NCI NIH HHS · CA-22677 · United States
NCI NIH HHS · CA-37156 · United States
External Links
PubMed source DOI: 10.1073/pnas.83.14.5233 PMC Full Text View journal details
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