Mouse fibroblast (type I) and immune (type II) interferons: pronounced differences in affinity for gangliosides and in antiviral and antigrowth effects on mouse leukemia L-1210R cells.

Abstract

Different interferons can be obtained from the same animal species depending on the cells and (or) the inducers used. Interferons of type I and type II differ not only antigenically but also in molecular weight and stability at low pH. We have investigated whether mouse type I and type II interferons also differ in properties relating to their biological action. We present evidence which suggests that the molecular mechanism leading to antiviral and antiowth effects induced by both types of interferon in susceptible cells must differ in at least one important step. Antiviral and antigrowth activities of type I but not of type II interferon are both inhibited when gangliosides are added to cell cultures together with the interferon. Whereas type I interferon strongly binds to ganglioside affinity columns and can be eluted with solutions of N-acetylneuraminyllactose, type II interferon passes through such columns unretarded.

Isolation and characterization of an interferon-resistant cell line deficient in the induction of (2'-5')oligoadenylate synthetase activity.

“…Hence, these cells may not be deficient in IFN receptors. This is in contrast to other variant cells, such as the mouse lymphoma L-1210(R) (8), which appears to be completely resistant to IFN due to a lack of receptors (2). An alternative explanation for the defect in A10 cells is the possible presence of two types of IFN receptors.…”

“…Briefly, cell extracts were prepared by lysing packed cells in an equal volume of 100 mM KCI, 10 mM Tris-hydrochloride (pH 7.6), 5 mM MgCI2, 0.5% Nonidet P-40, and 10%o glycerol, followed by a 10-min centrifugation at 15,000 x g. The supernatant was carefully removed and kept in small samples at -70°C. In a typical binding experiment, 25 F±l of cell extract was incubated at 0°C for 60 min in a final volume of 50 1RI with 32P-labeled probe: ppp(A2'p)3A32pCp (2,263 cpm per assay; a gift from I.M. Kerr, ICRF, United Kingdom) and 80 mM KCI, 9 mM MgC92, 0.7 mM dithiothreitol, 15 mM Tris-hydrochloride (pH 7.6), 2.5 mM ATP, and 7% glycerol.…”

Mouse Interferon Receptors: A Difference in Their Response to and beta Interferons

“…Human 7 interferon competes with neither ~ nor fl human interferons (Branca & Baglioni, 1981;Aguet et al, 1982), although in the reverse experiment, fl interferon will compete with ~, interferon, but ~ interferon will not (Anderson et al, 1982). The antiviral and antigrowth activities of both • and fl interferons are inhibited by gangliosides but neither of these activities of 7 interferon are so inhibited (Ankel et al, 1980). Estimates of the number of c~ or fl receptor sites per cell vary between 350 for human diploid and 550 for human trisomic fibroblasts (Epstein et al, 1982), 1000 for mouse L-1210S cells (Aguet & Blanchard, 1981) and 5000 for human lymphoblastoid cells (Branca & Baglioni, 1981).…”

“…It is postulated that ct and fl interferons bind to the same receptor because both ct and fl interferons can be inhibited by gangliosides (Ankel et al, 1980;Kushnaryev et al, 1983) and by each other (Aguet & Blanchard, 1981 ;Branca & Baglioni, 1981 ;Yonehara et al, 1983). The spectrum of biological activities of different human cc interferons varies in different cells (Weck et al, 1981), however, and binding and activity studies of the ct interferons (Hannigan et al, 1983) and of hybrid molecules derived from ct interferons (Streuli et al, 1981 ;Rehberg et al, [-1 V1 .-x.…”

Cross-resistance to Human Interferon- of Human Interferon-beta-resistant F-IFr Cells

“…Thus, F-IF r cells are less sensitive than RSa cells to the antiviral activity of all three types of IFN. According to Ankel et al (1980), mouse leukaemia L1210R cells, which are resistant to IFN-~/fl, are sensitive to mouse IFN-~. Likewise, murine sarcoma virus-transformed mouse cells which were selected for their resistance to the antiviral action of IFN-~/fl, were reported to be sensitive to mouse IFN-~ (Bourgeade et al, 1980).…”