Electrophoretically pure mouse interferon exerts multiple biologic effects.

Abstract

Electrophoretically pure mouse interferon was examined for a number of biologic effects previously ascribed to crude or partially purified interferon preparations. These effects include: inhibition of the growth of a transplantable tumor in mice; inhibition of cell multiplication of mouse tumor cells in vitro; enhancement of the expression of histocompatibility antigens on mouse tumor cells in vitro; inhibition of antibody formation in vitro; inhibition of sensitization to sheep erythrocytes and the expression of delayed type hypersensitivity in mice; enhancement of natural killer cell activity in vivo and in vitro; enhancement of cell sensitivity to the toxicity of poly(I)poly(C); and enhanced production ("priming") of interferon production in vitro. Our results establish that the molecules responsible for the antiviral action of interferon are also responsible for these varied biologic effects.In many animal cells, viral infection results in the production of potent antiviral glycoproteins called interferon (1). In addition to interferon's well-known antiviral action, preparations of it have been reported to exert multiple effects on cells [i.e., inhibition of the multiplication of bormal and tumor cells in culture (2-5), inhibition of the growth of a variety of transplantable tumors in mice (6-8), modulation of the synthesis and release of specific cellular products (9-16), modification of the cell surface (17-21), and modulation of both the humoral (22-27) and cell-mediated immune responses (28-34)]. Although experimental results support the hypothesis that the antiviral action of interferon is only one manifestation of its effect on cells (35-37), it is important to emphasize that these experiments were undertaken using preparations in which interferon protein constituted at most only 1% of the total protein content. We have recently succeeded in preparing electrophoretically pure (EP) mouse interferon (38), and we present herein results which show that a number of the biologic effects previously observed with crude or partially purified preparations are also observed with this EP interferon. These results provide the most direct evidence to date that interferon not only inhibits viral multiplication but also exerts a variety of important biologic effects on cells. MATERIALS AND METHODSPartially purified mouse interferon Mouse C-243 cell interferon was prepared, assayed, partially purified, and concentrated as described (39). The specific activity of the individual preparations ranged from 1 X 107 to 2.9 X 107 mouse interferon reference units/mg of protein. Electrophoretically pure (EP) mouse interferonMouse C-243 cell interferon was prepared as above but was kept for at least 2 weeks at pH 2 before purification. (It was not concentrated by precipitation with ammonium sulfate.) Purification was achieved by two-step affinity chromatography, first on a poly(U)-agarose column (40) and then on a column of sheep anti-mouse interferon globulin coupled to Affigel (38,41).We may summarize the criteria o...

Remission of leukemia and loss of feline leukemia virus in cats injected with Staphylococcus protein A: association with increased circulating interferon and complement-dependent cytotoxic antibody.

“…Just what role the IFN response plays in regression of the neoplastic disease and the virus infection and how its influence relates to the role of the cytotoxic antibody is unclear. Nonetheless, it is provocative to consider several properties of IFN that may be playing a role-i.e., its antiproliferative influences (17,18), its capacity to activate macrophages and other effector cells (19,20) that can inhibit neoplasia, and its increase of natural killer functions (21). Each of these possibilities needs investigation in future analyses.…”

“…Feline IFN was assayed by a modification of the microplaque reduction method (7), using approximately 40 plaque-forming units (pfu) of vesicular stomatitis virus (VSV) per well on FFC-9 cells (fetal cat fibroblast cell line kindly provided by N. C. Pedersen, University of California, Davis). An [21][22][23][24][25][26][27]1983, Kyoto, Japan (abstr. ).…”

Resistance to Interferon of a Human Adenocarcinoma Cell Line, HEC-1, and its Sensitivity to Natural Killer Cell Action

“…Interferons exhibit not only antiviral action, but various anticellular activities (Gresser, 1977a;Gresser et al, 1979). Interferons suppress the growth of cells by acting directly on them (Gresser, 1977 b;Gresser & Tovey, 1978) and at the same time indirectly by activating the cytotoxicity of natural killer cells (Trinchieri & Santoli, 1978;Herberman et al, 1979) or macrophages (Schultz & Chirigos, 1978).…”

Growth-promoting effect of oestriol in a lymphoma lacking oestrogen receptors

“…Furthermore, NK cells may also not be involved in this tumour model, because long-term exposure to oestrogens is required for the reduction of NK activity (Seaman et al, 1978). At the early stage of tumour growth, however, we cannot fully exclude the possibility that E3 inhibits the production of some antitumour factors in the tumour microenvironment, such as interferons (Seaman et al, 1979;Gresser et al, 1979;Uno et al, 1985), tumour necrosis factor (Carswell et al, 1975) or tumour degenerating factor (Tanaka et al, 1985).…”