Evidence that types I and II interferons have different receptors

Branca, Andrew A.; Baglioni, Corrado

doi:10.1038/294768a0

Cited by 479 publications

(178 citation statements)

References 21 publications

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“…This binding could be inhibited competitively by excess unlabeled rhuIFN-y (Fig . 2B), but not by IFNa2 (not shown), which interacts with distinct receptors (2) . Seven additional antibodies such as antibody A3 (Fig .…”

Section: Resultsmentioning

confidence: 99%

Purification of human gamma interferon receptors by sequential affinity chromatography on immobilized monoclonal antireceptor antibodies and human gamma interferon.

Aguet¹,

Merlin²

1987

The Journal of Experimental Medicine

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mAbs against human IFN-gamma (huIFN-gamma) receptors were obtained by immunizing a BALB/c mouse with eluates from immobilized recombinant huIFN-gamma (rhuIFN-gamma) on which lysates of enriched Raji cell membranes had been adsorbed. mAbs were selected for competitive inhibition of receptor binding of 125I-labeled rhuIFN-gamma. The following additional properties suggest that these antibodies are specific for huIFN-gamma receptors: they bind to the surface of human cells expressing IFN-gamma receptors but not to heterologous cells; this binding is inhibited competitively by addition of rhuIFN-gamma; the number of binding sites revealed by direct binding of 125I-labeled rhuIFN-gamma correlates with the amount of antigen recognized by the mAbs on different cell lines. A Triton X-100 extract of a membrane-enriched fraction of human Raji cells was affinity purified with these mAbs and the eluates from such columns were further purified on immobilized rhuIFN-gamma. As revealed by SDS-PAGE, the final eluate contained two major protein bands with approximate Mr of 90,000 (p90) and 50,000 (p50), respectively. Both proteins were able to specifically bind 125I-labeled rhuIFN-gamma upon electroblotting to nitrocellulose. This binding could be inhibited by the huIFN-gamma receptor mAbs, suggesting that the same epitopes are recognized on p90, p50, and on the cell surface. Therefore, these proteins most likely represent at least a part of huIFN-gamma receptors.

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Section: Resultsmentioning

confidence: 99%

Purification of human gamma interferon receptors by sequential affinity chromatography on immobilized monoclonal antireceptor antibodies and human gamma interferon.

Aguet¹,

Merlin²

1987

The Journal of Experimental Medicine

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“…Most of these studies have utilized probes that contain, at best, only 30% labeled IFN molecules [2,4,7,8,10,12,14,15,26,311. Since it remained likely that IFN receptor expression was incompletely described in these reports, we have characterized HuIFN-a2 receptor expression on human cells, using '251-labeled IFN-a2 iodinated to a mean incorporation of 90 -100%.…”

Section: Discussionmentioning

confidence: 99%

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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“…However, the intracellular mechanism(s) that mediate lFN-?,-induced responses have yet to be fully elucidated, particularly as it relates to the induction of cell differentiation. Increasing evidence supports a role for arachidonic acid (AA) metabolites in the control of neuronal cell differentiation and, although IFN-2" initiates its action through binding to a specific receptor distinct from that recognizing IFN-~/fl [10], very recently it has been shown that IFN-~ induced the tran-sient activation of phospholipase A.~ (PLA,.) in 3T3 fibroblasts [11].…”

Section: Fn-7' a Lymphokine Produced By Activated T Lymphocytes Andmentioning

confidence: 99%

Stimulation of receptor‐coupled phospholipase A₂ by interferon‐γ

1992

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The biomolecular mechanisms that mediate signal transduction by type 11 (γ) interferon (IFN) are poorly understood. IFN‐γ is a potent growth inhibitory cytokine also endowed with antiviral, immunomodulatory, and differentiating activities on various cell targets, including neural cells. IFN‐γ induced a rapid and transient activation of phospholipase A2 in LAN‐5, a human neuroblastoma cell line. A consequence of phospholipase A2 activation was the release of arachidonic acid and the generation of lysophospholipids from membrane phospholipids. Treatment of pre‐labeled LAN‐5 cells with a receptor‐saturating concentration of IFN‐γ led to a time‐dependent release of [3H]arachidonic acid into the culture media and generation or [32P]lysophosphatidylcholine. Pretreatment of cultures with the phospholipase A2 inhibitor, bromophenacyl bromide, markedly inhibited both [3H]arachidonic acid release and lysophosphatidylcholine production induced by IFN‐γ treatment. Pretreatment of LAN‐5 cells with nordihydroguaiaretic acid, a lipoxygenase inhibitor, or with indomethacin, a cyclooxygenase inhibitor, amplified the release of[3H]arachidonic acid and production of lysophosphatidylcholine induced by non‐saturating concentrations of IFN‐γ. In parallel, and with the same time‐dependent effect, a significant decrease in phosphatidylcholine labeling was observed in IFN‐γ‐treated cells, further indicating that a potential signal transduction mechanism of IFN‐γ is the hydrolysis of membrane phosphatidylcholine by phospholipase A2.

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Evidence that types I and II interferons have different receptors

Cited by 479 publications

References 21 publications

Purification of human gamma interferon receptors by sequential affinity chromatography on immobilized monoclonal antireceptor antibodies and human gamma interferon.

Purification of human gamma interferon receptors by sequential affinity chromatography on immobilized monoclonal antireceptor antibodies and human gamma interferon.

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

Stimulation of receptor‐coupled phospholipase A₂ by interferon‐γ

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Evidence that types I and II interferons have different receptors

Cited by 479 publications

References 21 publications

Purification of human gamma interferon receptors by sequential affinity chromatography on immobilized monoclonal antireceptor antibodies and human gamma interferon.

Purification of human gamma interferon receptors by sequential affinity chromatography on immobilized monoclonal antireceptor antibodies and human gamma interferon.

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

Stimulation of receptor‐coupled phospholipase A2 by interferon‐γ

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Stimulation of receptor‐coupled phospholipase A₂ by interferon‐γ