Similarities of Murine Gamma Interferon and the Lymphokine that Renders Macrophages Cytotoxic

Kleinschmidt, W. J.; Schultz, Richard M.

doi:10.1089/jir.1982.2.291

Cited by 51 publications

(22 citation statements)

References 13 publications

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“…(iv) The ratio between the priming and antiviral activities in the hybridoma culture supernate was indistinguishable from that determined for recombinant mouse IFN-y. Recent reports by others showing that the priming and antiviral activities in culture supernates of mixed spleen cell populations are associated (15), or even copurify (16), further support our conclusion.…”

Section: Discussionsupporting

confidence: 89%

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Macrophage activation: priming activity from a T-cell hybridoma is attributable to interferon-gamma.

Pace¹,

Russell²,

Schreiber³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

165

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Antiviral and macrophage-priming activities in the supernatant medium of a subelone of a concanavalin A-stimulated mouse T-cell hybridoma were investigated. The two activities were associated with a molecular weight of approximately 50,000 and could not be separated by various approaches. Both activities were eliminated by a highly specific neutralizing antibody against mouse interferon-v, but not by antibody against interferon-a and -(P. The ratio of-priming to antiviral activity in the hybridoma culture supernate was indistinguishable from the ratio obtained with mouse interferon-yprepared by recombinant DNA technology. It was concluded from these data that the priming activity in hybridoma culture supernates was attributable to interferon-and that this mediator is one form of the lymphokine macrophage-activating factor. Interferon-y was greater than 800 times more efficient at priming mouse macrophages for tumor cell killing than was a mixture of interferon-a and -(3. This finding contributes to growing awareness that type II interferon may have greater immunoregulatory potential than type I interferons.Macrophages can be activated to kill tumor cells in vitro by a nonspecific, extracellular mechanism that may be important in host defense against neoplastic cells in vivo. An important goal, therefore, is acquisition of better understanding of how the process of activation is regulated. Recently, it has been shown that under defined conditions the lymphokine macrophage-activating factor (MAF) does not render macrophages fully cytolytic (1-5). Instead, it heightens their responsiveness to a second signal(s) that then triggers the expression of killing-i.e., MAF "primes" macrophages to respond to a second, triggering stimulus.A cloned hybridoma (24/Gl) has been recognized that produces MAF, identified by its ability to prime mouse macrophages for tumor cell killing (6). The hybridoma-derived MAF was shown by various biochemical and functional criteria to be indistinguishable from conventionally prepared MAF (6). These supernates also contained antiviral activity attributed to interferon (IFN)-y.We report here that the antiviral and macrophage-priming activities produced by cells of a subclone of 24/Gl are not dissociable by various approaches. These results, together with data obtained by using recombinant mouse IFN-y, support a conclusion that priming activity produced by this hybridoma is attributable to IFN-y. We also report here that IFN-y is much more potent as a macrophage priming agent than type I interferon is. MATERIALS AND METHODSMice. Male C3H/HeN mice were obtained from Charles River Breeding Laboratories (Kingston, NY) and used at 6-9 weeks of age.

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Section: Discussionsupporting

confidence: 89%

“…Certainly, attention has previously been called to the striking functional and physicochemical similarities that exist between these two mediators (15,25), and the fact that they copurify (ref. 16; unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Macrophage activation: priming activity from a T-cell hybridoma is attributable to interferon-gamma.

Pace¹,

Russell²,

Schreiber³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

165

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“…On the other hand, the antitumour activity of Ge-132 appears to involve MO, since the administration of MO blockers prevented the expression of the antitumour activity of Ge-132 (Suzuki, 1985a), the passive transfer of MO from Ge-mice conferred antitumour resistance to untreated tumour-bearing mice (Suzuki, 1985b), and MO from Ge-Mice also had cytotoxic properties in vitro against certain tumours which were sensitive to the antitumour activity of Ge-132 in vivo (Suzuki, 1985b). Some reports (Kleinschmidt & Schultz, 1982;Robert & Vasil, 1982) suggest that the induction of tumouricidal MO from a resting state requires IFN y which induced the priming step (Pace et al, 1982) in MO activation, or acts as a cofactor associated with M4-activating factor (Mannel & Falk, 1983). In addition, it was also demonstrated that the in vivo administration of anti-Thyl.2 mAb, effectively prevented the expression of antitumour activity of Ge-1 32 761 (Suzuki, 1985a).…”

Section: Discussionmentioning

confidence: 99%

Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours

Suzuki¹,

Brutkiewicz²,

Pollard³

1985

Br J Cancer

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Sera from C57Bl/6 mice treated orally with Ge-132 exhibited antitumour activity against Ehrlich (allogeneic) and RL male 1 (syngeneic) ascites tumours in BALB/c mice. Sera obtained from mice 24 h after Ge-132 administration displayed the greatest antitumour effect and this was dose dependent. Sera prepared from mice 12, 36, or 48 h after Ge-132 treatment had no protective effect. Circulating interferon (IFN) was induced at 24 h after administration of Ge-132 but was not detected in the sera at 12, 36, or 48 h after administration. The antiviral activity of sera from Ge-132-treated mice was inactivated by treatments with trypsin, low pH, and anti-IFN gamma antiserum. The inactivated preparations of serum IFN induced by Ge-132 did not exhibit antitumour activity when administered to tumour-bearing mice. These results suggest that antitumour activity in the sera of Ge-132-treated mice may be expressed through activities of Ge-132-induced lymphokine(s), such as IFN gamma.

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“…Lymphokines released by antigen-or mitogen-stimulated lymphocytes contain significant IFN-T activity [21,22,37,38]. Recent attention has focused on the immunoregulating role of IFN-T with respect to modulating the activity of natural killer (NK) cells [6,14,16,17] and macrophages [7, 11, 21, 22, 25, 27, 32, 3 5 -3 8 , 41, 42].…”

Section: Introductionmentioning

confidence: 99%

Potentiation of direct antitumor cytotoxicity and production of tumor cytolytic factors in human blood monocytes by human recombinant interferon-gamma and muramyl dipeptide derivatives

Sone

López-Berestein

Fidler

1986

Cancer Immunol Immunother

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We investigated whether human peripheral blood monocytes isolated by centrifugal elutriation from healthy donors could be activated to become tumoricidal and release tumor cytolytic factor (TCF) subsequent to incubation with recombinant human interferon-gamma (r-IFN-gamma) or a derivative of muramyl dipeptide (nor-MDP), or both. Blood monocytes incubated in endotoxin-free medium containing up to 1000 U/ml of r-IFN-gamma or in medium containing less than 1 microgram/ml of nor MDP were not activated to lyse radiolabeled allogeneic human tumor cells. In contrast, the incubation of monocytes with various dose combinations of r-IFN-gamma and nor-MDP generated significant direct cytotoxic activity as well as production of TCF. Preincubation of the r-IFN-gamma and nor-MDP mixture with polymyxin B did not inhibit the synergism, thus ruling out the possibility that the process was due to endotoxin contamination. TCF harvested from monocyte culture supernatants was cytolytic against five allogeneic tumor targets, but not against a nontumorigenic cell line. Collectively, the data demonstrate that r-IFN-gamma can prime human blood monocytes to allow their activation by synthetic nor-MDP.

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Similarities of Murine Gamma Interferon and the Lymphokine that Renders Macrophages Cytotoxic

Cited by 51 publications

References 13 publications

Macrophage activation: priming activity from a T-cell hybridoma is attributable to interferon-gamma.

Macrophage activation: priming activity from a T-cell hybridoma is attributable to interferon-gamma.

Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours

Potentiation of direct antitumor cytotoxicity and production of tumor cytolytic factors in human blood monocytes by human recombinant interferon-gamma and muramyl dipeptide derivatives

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