Production of high levels of human leukocyte interferon from a continuous human myeloblast cell culture

Familletti, Philip C.; McCandliss, Russell; Pestka, Sidney

doi:10.1128/aac.20.1.5

Cited by 28 publications

(14 citation statements)

References 39 publications

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“…This had been accomplished several years earlier when IFN mRNA was translated in cell-free extracts (30,31) and in frog oocytes (32)(33)(34). The next step was to prepare sufficient mRNA from cells synthesizing IFN, and this was accomplished with both fibroblasts and leukocytes (35,36). A library of complementary DNA (cDNA) was prepared from a template of partially purified mRNA isolated from human leukocytes synthesizing IFN.…”

Section: Cloning Recombinant Human Ifn-␣ and Ifn-␤mentioning

confidence: 99%

The Interferons: 50 Years after Their Discovery, There Is Much More to Learn

Pestka

2007

Journal of Biological Chemistry

348

255

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Section: Cloning Recombinant Human Ifn-␣ and Ifn-␤mentioning

confidence: 99%

The Interferons: 50 Years after Their Discovery, There Is Much More to Learn

Pestka

2007

Journal of Biological Chemistry

348

255

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“…Purification of multiple species was also accomplished with interferon produced by a continuous cell line, KG-I, which had been established from a patient with erythroleukemia [16]. Initial work in our laboratory demonstrated that KG-l was a good producer of interferon after proper growth and induction [17,18]. Eventually, eight major species of human interferon were purified from these cells [19].…”

Section: Purification and Properties Of Natural Leukocyte Interferonsmentioning

confidence: 99%

Purification, Bacterial Expression, and Biological Activities of the Human Interferons

Langer

Pestka

1984

Journal of Investigative Dermatology

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The structural and functional complexity of the hu man interferon system has become increasingly evident. More than eight different alpha (leukocyte) interferons are expressed in induced human cells in culture. Many of these have been purified by a combination of methods, including high-performance liquid chromatography. Moreover, at least 12 different human leukocyte inter ferons have been cloned, and several have been effi ciently expressed in Escherichia coli and other orga nisms. The availability of purified species of leukocyte interferon, both natural and recombinant, has allowed structural work to be done, including amino acid se quence determinations, chemical modification studies, and the crystallization of one species. The purified ma terial has also been used for the production of mono clonal antibodies with various specificities that are proving invaluable in rapid assays and purification techniques. Testing of the purified species for their rel ative potency in antiviral, antiproliferative, and immu nomodulatory assays has begun to demonstrate the func tional uniqueness and diversity of the purified alpha interferons. Hybrid interferon genes have been synthe sized by splicing together parts of various cloned inter feron genes. The resulting hybrid proteins have been valuable in establishing structure/function relation ships. In several cases, the functional properties of the hybrid protein were novel and unpredicted from the properties of the parental molecules.Interferon was discovered by Isaacs and Lindenmann during an investigation of the phenomenon of viral interference, wherein infection by one virus produces resistance to subse quent infection by other, apparently unrelated viruses. Their work [1,2] and that of others [3] demonstrated that cells could respond to challenge with a virus or with other substances (subsequently termed inducers) by producing a substance that could confer upon other cells resistance to subsequent viral attack. This substance, termed interferon, was characterized as a protein that had some species specificity, but that was fairly nonspecific in protecting against a wide range of viruses.Since that time, the complexity of the system has increased as more interferon species within an organism have been rec ognized and characterized and biological effects have beenThe chemical heterogeneity of the interferons has become increasingly evident (Table I). It was found that interferons produced by different cell types were either stable or labile at pH 2. This lead to the designation of types I and II, respectively.Further work demonstrated that there were two main antigen-

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“…They are mainly produced by virus-infected peripheral blood leukocytes, lymphoblastoid and myeloblastoid cell lines (Familletti et al, 1981). The human IFN-α gene cluster is distributed over approximately 400 kb on the short arm of chromosome 9, and consists of at least thirteen IFN-α genes and one IFN-α pseudogene (Diaz et al, 1994;Hardy et al, 2004).…”

Section: Introductionmentioning

confidence: 99%