{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:48:50Z","timestamp":1760204930642},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[1991,6,1]],"date-time":"1991-06-01T00:00:00Z","timestamp":675734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1991,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Conditioned medium (CM) from cultures of cytotoxic activated macrophages causes inhibition of mitochondrial respiration, DNA synthesis, and aconitase activity in murine EMT-6 mammary adenocarcinoma cells by an l-arginine dependent effector mechanism. CM induces cytotoxicity and nitrite synthesis in EMT-6 cells in a dose dependent manner. We have identified the soluble factors in CM that induce cytotoxicity and synthesis of inorganic nitrogen oxides from l-arginine by EMT-6 cells. Using functional inhibition experiments, the activity of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF\u03b1), and interferon gamma (IFN\u03b3) in CM was investigated. The LPS inhibitor polymyxin B and TNF\u03b1 antibody produced a modest decrease in nitrite production, while IFN\u03b3 antibody markedly inhibited both nitrite production and cytostasis. Simultaneous treatment with polymyxin B, TNF\u03b1 antibody, and IFN\u03b3 antibody reduced EMT-6 cell nitrite production by 81%, and cytostasis by 74%. By Western blot, IFN\u03b3 and TNF\u03b1 were shown to be present in CM. When CM was subjected to hydrophobic interaction chromatography, a single peak of activity was eluted, and Western blot showed that the active fractions contained IFN\u03b3. Furthermore, IFN\u03b3 antibody neutralized the activity in these chromatographic fractions. We conclude that induction of inorganic nitrogen oxide synthesis from l-arginine by the synergistic combination of IFN\u03b3, TNF\u03b1, and LPS accounts for most of the biologic activity of CM, and that IFN\u03b3 is the major priming factor.<\/jats:p>","DOI":"10.1002\/jlb.49.6.610","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T19:48:49Z","timestamp":1515786529000},"page":"610-620","source":"Crossref","is-referenced-by-count":43,"title":["Activated Macrophage Conditioned Medium: Identification of the Soluble Factors Inducing Cytotoxicity and the L-Arginine Dependent Effector Mechanism"],"prefix":"10.1093","volume":"49","author":[{"given":"Ina J","family":"Amber","sequence":"first","affiliation":[{"name":"Veterans Administration Medical Center and the Department of Medicine, Divisions of Human Development and Aging, Infectious Diseases, and Hematology\/Oncology, University of Utah School of Medicine , Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John B","family":"Hibbs","sequence":"additional","affiliation":[{"name":"Veterans Administration Medical Center and the Department of Medicine, Divisions of Human Development and Aging, Infectious Diseases, and Hematology\/Oncology, University of Utah School of Medicine , Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles J","family":"Parker","sequence":"additional","affiliation":[{"name":"Veterans Administration Medical Center and the Department of Medicine, Divisions of Human Development and Aging, Infectious Diseases, and Hematology\/Oncology, University of Utah School of Medicine , Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara B","family":"Johnson","sequence":"additional","affiliation":[{"name":"Veterans Administration Medical Center and the Department of Medicine, Divisions of Human Development and Aging, Infectious Diseases, and Hematology\/Oncology, University of Utah School of Medicine , Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Read R","family":"Taintor","sequence":"additional","affiliation":[{"name":"Veterans Administration Medical Center and the Department of Medicine, Divisions of Human Development and Aging, Infectious Diseases, and Hematology\/Oncology, University of Utah School of Medicine , Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zdenek","family":"Vavrin","sequence":"additional","affiliation":[{"name":"Veterans Administration Medical Center and the Department of Medicine, Divisions of Human Development and Aging, Infectious Diseases, and Hematology\/Oncology, University of Utah School of Medicine , Salt Lake City"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1991,6,1]]},"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjlb.49.6.610","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/49\/6\/610\/49767202\/jlb0610.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/49\/6\/610\/49767202\/jlb0610.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T08:49:11Z","timestamp":1681202951000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/49\/6\/610\/6977598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,6,1]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1991,6,1]]},"published-print":{"date-parts":[[1991,6,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.49.6.610","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1991,6]]},"published":{"date-parts":[[1991,6,1]]}}}