Effect of recombinant human tumor necrosis factor on the induction of murine macrophage tumoricidal activity

The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exudate cells (PEC) with rH-TNF and LK was found to induce the activ...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 1987-06, Vol.47 (11), p.2793-2798
Hauptverfasser: HORI, K, EHRKE, M. J, MACE, K, MACCUBIN, D, DOYLE, M. J, OTSUKA, Y, MIHICH, E
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container_end_page 2798
container_issue 11
container_start_page 2793
container_title Cancer research (Chicago, Ill.)
container_volume 47
creator HORI, K
EHRKE, M. J
MACE, K
MACCUBIN, D
DOYLE, M. J
OTSUKA, Y
MIHICH, E
description The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exudate cells (PEC) with rH-TNF and LK was found to induce the activation of macrophages to a tumoricidal state against P815 mastocytoma cells. Neither rH-TNF nor LK alone induced macrophage cytotoxic activity. Furthermore, the macrophage activation seen was not due to small amounts of contaminating lipopolysaccharide. The TNF plus LK-mediated macrophage activation could be totally ablated by rabbit antiserum to murine gamma-interferon, thus suggesting a role for gamma-interferon in this system. Since adherent cells (greater than or equal to 95% macrophages) only marginally responded to stimulation with rH-TNF plus LK and the addition of nonadherent PEC caused a marked augmentation of rH-TNF plus LK-mediated macrophage activation, the involvement of nonadherent PEC was suggested. In addition, using antibodies and complement to deplete subsets of cells from the nonadherent PEC, the requirement for cells bearing Thy 1.2 and asialo GM1 surface markers was demonstrated. These results suggest that TNF may play an autocrine regulatory role in concert with lymphokines in macrophage-mediated host defense against malignant neoplasia.
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J ; MACE, K ; MACCUBIN, D ; DOYLE, M. J ; OTSUKA, Y ; MIHICH, E</creator><creatorcontrib>HORI, K ; EHRKE, M. J ; MACE, K ; MACCUBIN, D ; DOYLE, M. J ; OTSUKA, Y ; MIHICH, E</creatorcontrib><description>The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exudate cells (PEC) with rH-TNF and LK was found to induce the activation of macrophages to a tumoricidal state against P815 mastocytoma cells. Neither rH-TNF nor LK alone induced macrophage cytotoxic activity. Furthermore, the macrophage activation seen was not due to small amounts of contaminating lipopolysaccharide. The TNF plus LK-mediated macrophage activation could be totally ablated by rabbit antiserum to murine gamma-interferon, thus suggesting a role for gamma-interferon in this system. Since adherent cells (greater than or equal to 95% macrophages) only marginally responded to stimulation with rH-TNF plus LK and the addition of nonadherent PEC caused a marked augmentation of rH-TNF plus LK-mediated macrophage activation, the involvement of nonadherent PEC was suggested. In addition, using antibodies and complement to deplete subsets of cells from the nonadherent PEC, the requirement for cells bearing Thy 1.2 and asialo GM1 surface markers was demonstrated. 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J</creatorcontrib><creatorcontrib>OTSUKA, Y</creatorcontrib><creatorcontrib>MIHICH, E</creatorcontrib><title>Effect of recombinant human tumor necrosis factor on the induction of murine macrophage tumoricidal activity</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exudate cells (PEC) with rH-TNF and LK was found to induce the activation of macrophages to a tumoricidal state against P815 mastocytoma cells. Neither rH-TNF nor LK alone induced macrophage cytotoxic activity. Furthermore, the macrophage activation seen was not due to small amounts of contaminating lipopolysaccharide. The TNF plus LK-mediated macrophage activation could be totally ablated by rabbit antiserum to murine gamma-interferon, thus suggesting a role for gamma-interferon in this system. Since adherent cells (greater than or equal to 95% macrophages) only marginally responded to stimulation with rH-TNF plus LK and the addition of nonadherent PEC caused a marked augmentation of rH-TNF plus LK-mediated macrophage activation, the involvement of nonadherent PEC was suggested. In addition, using antibodies and complement to deplete subsets of cells from the nonadherent PEC, the requirement for cells bearing Thy 1.2 and asialo GM1 surface markers was demonstrated. These results suggest that TNF may play an autocrine regulatory role in concert with lymphokines in macrophage-mediated host defense against malignant neoplasia.</description><subject>Animals</subject><subject>Antigens, Surface - analysis</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Cytotoxicity, Immunologic</subject><subject>Dose-Response Relationship, Drug</subject><subject>G(M1) Ganglioside</subject><subject>Glycoproteins - pharmacology</subject><subject>Glycosphingolipids - analysis</subject><subject>Humans</subject><subject>Interferon-gamma - physiology</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Lymphokines - pharmacology</subject><subject>Macrophage Activation - drug effects</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neoplasms, Experimental - immunology</subject><subject>Other treatments</subject><subject>Peritoneal Cavity - cytology</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Thy-1 Antigens</subject><subject>Time Factors</subject><subject>Treatment. 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J</au><au>OTSUKA, Y</au><au>MIHICH, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of recombinant human tumor necrosis factor on the induction of murine macrophage tumoricidal activity</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>1987-06-01</date><risdate>1987</risdate><volume>47</volume><issue>11</issue><spage>2793</spage><epage>2798</epage><pages>2793-2798</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exudate cells (PEC) with rH-TNF and LK was found to induce the activation of macrophages to a tumoricidal state against P815 mastocytoma cells. Neither rH-TNF nor LK alone induced macrophage cytotoxic activity. Furthermore, the macrophage activation seen was not due to small amounts of contaminating lipopolysaccharide. The TNF plus LK-mediated macrophage activation could be totally ablated by rabbit antiserum to murine gamma-interferon, thus suggesting a role for gamma-interferon in this system. Since adherent cells (greater than or equal to 95% macrophages) only marginally responded to stimulation with rH-TNF plus LK and the addition of nonadherent PEC caused a marked augmentation of rH-TNF plus LK-mediated macrophage activation, the involvement of nonadherent PEC was suggested. In addition, using antibodies and complement to deplete subsets of cells from the nonadherent PEC, the requirement for cells bearing Thy 1.2 and asialo GM1 surface markers was demonstrated. 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ispartof Cancer research (Chicago, Ill.), 1987-06, Vol.47 (11), p.2793-2798
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source MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals
subjects Animals
Antigens, Surface - analysis
Biological and medical sciences
Cells, Cultured
Cytotoxicity, Immunologic
Dose-Response Relationship, Drug
G(M1) Ganglioside
Glycoproteins - pharmacology
Glycosphingolipids - analysis
Humans
Interferon-gamma - physiology
Lipopolysaccharides - pharmacology
Lymphokines - pharmacology
Macrophage Activation - drug effects
Macrophages - drug effects
Macrophages - immunology
Medical sciences
Mice
Neoplasms, Experimental - immunology
Other treatments
Peritoneal Cavity - cytology
Recombinant Proteins - pharmacology
Thy-1 Antigens
Time Factors
Treatment. General aspects
Tumor Necrosis Factor-alpha
Tumors
title Effect of recombinant human tumor necrosis factor on the induction of murine macrophage tumoricidal activity
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