Treatment of lymphoblastoid cells with interferon decreases insulin binding

Faltynek, Connie R.; McCandless, Sarah; Baglioni, Corrado

doi:10.1002/jcp.1041210224

Cited by 29 publications

(8 citation statements)

References 18 publications

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“…Furthermore, dissociation kinetics [13] clearly support the concept of negatively cooperative interactions during IFN-a2 binding reactions. Thus, our present work accounts for and extends the observations made by these authors [31] and confirms a higher level of complexity in the interaction of IFN and cellular receptors than that of a simple bimolecular reaction.…”

supporting

confidence: 90%

“…Our conclusions regarding the nature of the IFN -receptor interaction are at variance with recent results reported by Faltynek et al [31]. These authors used competitive displacement analysis to conclude that IFN-a2 interacts with cellular receptors in a simple bimolecular interaction characterized by a Kd of (2-3) x lo-'" M, with binding at 4°C.…”

contrasting

confidence: 48%

“…3) is apparent. Since our probes discriminate both linear and curvilinear Scatchard plots, dependent on the growth status of the cells, it is unlikely that ligand-label heterogeneity is causing the biphasic Scatchard analysis, as invoked by Faltynek et al [31]. Furthermore, dissociation kinetics [13] clearly support the concept of negatively cooperative interactions during IFN-a2 binding reactions.…”

mentioning

confidence: 63%

“…These authors used competitive displacement analysis to conclude that IFN-a2 interacts with cellular receptors in a simple bimolecular interaction characterized by a Kd of (2-3) x lo-'" M, with binding at 4°C. The experimental design employed by Faltynek et al [31], in which all binding is measured at 251-IFN-cr2 concentrations above 70 pM, is inadequate to assess cooperative interactions in which a high-affinity interaction of Kd < 7 x lo-" M (Fig. 3) is apparent.…”

mentioning

confidence: 99%

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Differential human interferon alpha receptor expression on proliferating and non-proliferating cells

1986

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The expression of interferon-a (IFN-a) receptors was studied on a variety of human cells, using monoiodinated IFN-a2 probes. Steady-state binding at 4°C revealed a single class of non-interacting IFN receptor on peripheral blood lymphocytes, and tonsillar B lymphocytes, which are both known to be Go/G1 resting cell populations. The binding affinity of this class of receptor was found to be on the order of 5 x lo-'' M, expressed as an apparent dissociation constant (&). However, cells proliferating either in culture or in vivo were found to express a heterogeneity in IFN-cr2 binding. Such binding could be objectively resolved (by a version of the LIGAND program of P. Munson) into a two-site receptor model. Hill plots of binding to proliferating cells indicated a negative cooperativity in the interaction of IFN and receptor. The high-affinity component, expressed on proliferating cells, typically exhibits a Kd of (1 -10) x lo-" M, while the lower-affinity component indicates a Kd of (1 -10) x M. Furthermore, the low-affinity component is apparently expressed on the order of 10 -200 times the copy number, per cell, of the high-affinity site. Affinity-labeling experiments revealed that, in addition to the 140 -160-kDa IFN-binding complex reported by others, both the proliferating and non-proliferating cell populations possess a novel IFN-binding component of 60 kDa.The antiviral, antiproliferative and immunomodulating effects of interferons (IFNs) are mediated initially through the interaction of the interferon (a, jl or y type) with highaffinity plasma membrane receptors (reviewed in [l]). A number of studies using radiolabeled IFN-a, IFN-P and IFN-y suggest that IFN-a and IFN-P interact with a common cellular binding site, while IFN-y is recognized by a distinct receptor [2 -61. This conclusion is further supported by affinity-labeling experiments, which identify IFN-a-binding complexes of 140-160 kDa [4,7, 81, and IFN-y-binding complexes of about 110 kDa [6, 91, Similarities are evident in a comparison of the receptor interactions of many polypeptide hormones and growth factors, and the interaction of IFNs with their receptors. These similarities include ligand-induced down-regulation of receptors [S, 12, Recently we described a regulatory feature of IFN-a binding to human lymphoblastoid cells, which is consistent with a model of negative cooperativity [13] as originally described by DeMeyts for insulin -receptor interaction [17]. Heterogeneous binding, in the form of biphasic Scatchard plots of IFN-cr binding to Daudi lymphoblastoid cells, correlated with dissociation kinetics descriptive of negative cooperativity, also observed in a number of hormone receptor systems (see [18]). Further to this finding we now report that heterogeneous binding of IFN-a to human cells seems to be a function of receptor expression on actively proliferating cells, as opposed to non-proliferating cells, which exhibit homogeneous, noncooperative IFN-a binding over the range of ligand employed. Analysis of binding data by the LIGA...

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supporting

confidence: 90%

contrasting

confidence: 48%

mentioning

confidence: 63%

mentioning

confidence: 99%

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Differential human interferon alpha receptor expression on proliferating and non-proliferating cells

1986

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“…The EGF receptor's affinity for the ligand remained the same with or without IFN treatment, decreasing the possibility that IFN changed the EGF-receptor affinity state from high to low. These data are in agreement with previous reports demonstrating that pretreatment of lymphoblastoid Daudi cells with IFN-a2 resulted in a marked decrease in insulin binding with no decrease in receptor affinity (Pfeffer et al, 1987;Faltynek et al, 1984). While the Scatchard analysis (Fig.…”

Section: Inhibitory Effects Of Ifn On Egf-inducedsupporting

confidence: 94%

Interferon α/β modulation of growth‐factor‐stimulated mitogenicity in AKR‐2B fibroblasts

Pietenpol

Howe

Cunningham

et al. 1989

Journal Cellular Physiology

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Growth factor-stimulated mitogenicity in mouse embryo-derived AKR-2B cells was inhibited in a dose-dependent fashion by a mixture of alpha and beta mouse interferons (IFN). A 60% decrease in epidermal growth factor (EGF) and insulin-stimulated DNA synthesis was observed with 10 kU/ml IFN, and half-maximal inhibition was seen at 1 kU/ml. Likewise, the mitogenic effect of 5% fetal bovine serum (FBS) was inhibited by 60% with 10 kU/ml IFN and by 38% with 1 kU/ml IFN. IFN inhibition of DNA synthesis was paralleled by a decrease in monolayer growth of AKR-2B cells by 60% on the 3rd day of culture and by 40% on the 6th day of culture. Soft agar growth of two AKR-2B derived lines, AKR-MCA and AKR-2B (clone 84A), was also inhibited significantly with the addition of 1-10 kU/ml of IFN. The effect of IFN on EGF receptors was also examined. Treatment of AKR-2B cells with 10 kU/ml IFN resulted in a 35% decrease in EGF binding to cell surface receptors. The reduced binding of EGF to cells treated with IFN was due to a loss of EGF receptors as determined by Scatchard analysis. IFN treatment of AKR-2B cells neither altered the affinity of the EGF receptor for its ligand nor affected receptor internalization. Nuclear transcription and actinomycin D decay analysis indicated that within 2 hr, IFN reduced c-myc messenger RNA levels at the level of transcription with no affect on message decay.

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Anti‐proliferative effects of interferons on Daudiburkitt Lymphoma cells: Induction of cell differentiation and loss of response to autocrine growth factors

Exley

Gordon

Nathan

et al. 1987

Intl Journal of Cancer

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Treatment of Daudi B-lymphoblastoid cells with low concentrations of either natural or recombinant human alpha-interferons inhibits cell proliferation and modulates the expression of a number of cell-surface antigens. Using a panel of monoclonal antibodies (MAbs) identifying determinants expressed at the surface of normal plasma cells, and polyclonal antibodies against surface and cytoplasmic immunoglobulin, we have found that growth inhibition is accompanied by plasmacytoid differentiation. Assays of growth stimulation of heterologous cells indicate that the culture medium from interferon-treated Daudi cells contains substantially more B-cell growth factor activity than that from control cells. However, the interferon-treated cells exhibit an impaired ability to respond to both these autocrine factors and exogenous factors produced by another Burkitt lymphoma line. These findings show that, in the case of Daudi cells, growth inhibition by interferons is closely associated with both terminal differentiation and a refractoriness to growth factors. In this system IFN-alpha may therefore be considered to be a B-cell differentiation factor, suggesting a possible basis for the anti-proliferative effects observed with certain human B-cell malignancies.

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Treatment of lymphoblastoid cells with interferon decreases insulin binding

Cited by 29 publications

References 18 publications

Differential human interferon alpha receptor expression on proliferating and non-proliferating cells

Differential human interferon alpha receptor expression on proliferating and non-proliferating cells

Interferon α/β modulation of growth‐factor‐stimulated mitogenicity in AKR‐2B fibroblasts

Anti‐proliferative effects of interferons on Daudiburkitt Lymphoma cells: Induction of cell differentiation and loss of response to autocrine growth factors

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