PMID- 3487788 OWN - NLM STAT- MEDLINE DCOM- 19860820 LR - 20201216 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 83 IP - 14 DP - 1986 Jul TI - Tumor necrosis factor: a potent effector molecule for tumor cell killing by activated macrophages. PG - 5233-7 AB - 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. FAU - Urban, J L AU - Urban JL FAU - Shepard, H M AU - Shepard HM FAU - Rothstein, J L AU - Rothstein JL FAU - Sugarman, B J AU - Sugarman BJ FAU - Schreiber, H AU - Schreiber H LA - eng GR - CA-19266/CA/NCI NIH HHS/United States GR - CA-22677/CA/NCI NIH HHS/United States GR - CA-37156/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Glycoproteins) RN - 0 (Lymphotoxin-alpha) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Cytotoxicity, Immunologic/drug effects MH - Drug Resistance MH - Glycoproteins/pharmacology/*therapeutic use MH - Humans MH - Lymphotoxin-alpha/pharmacology MH - *Macrophage Activation MH - Mice MH - Mice, Inbred C3H MH - Neoplasms, Experimental/*drug therapy MH - Recombinant Proteins/pharmacology MH - Tumor Necrosis Factor-alpha PMC - PMC323925 EDAT- 1986/07/01 00:00 MHDA- 1986/07/01 00:01 PMCR- 1987/01/01 CRDT- 1986/07/01 00:00 PHST- 1986/07/01 00:00 [pubmed] PHST- 1986/07/01 00:01 [medline] PHST- 1986/07/01 00:00 [entrez] PHST- 1987/01/01 00:00 [pmc-release] AID - 10.1073/pnas.83.14.5233 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1986 Jul;83(14):5233-7. doi: 10.1073/pnas.83.14.5233.