Interferon-Like Virus-Inhibitor Induced in Human Leukocytes by Phytohemagglutinin

Wheelock, E F

doi:10.1126/science.149.3681.310

Cited by 645 publications

(276 citation statements)

References 11 publications

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“…It is conceivable that the blastic transformation of the lymphocyte in culture is associated with a derepression of a genetic locus normally expressed in other cell types. Derepression has been suggested as an explanation for the synthesis of interferon both in lymphoblast cell lines (16) and in PHA-stimulated lymphocytes (17) and for the production of multiple types of immunoglobulins by cloned lymphocytes in long-term culture (18). Also, in the case of malate dehydrogenase, there is evidence that a specific isoenzyme can be selectively synthesized in PHA-stimulated lymphocytes (19) …”

Section: Discussionmentioning

confidence: 99%

Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture.

Mitchell¹,

Haigis²,

Steinmann³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

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Stimulation with phytohemagglutinin of the leukocytes from six of the seven known individuals with UDP-galactose 4-epimerase (= UDP-glucose 4-epimerase; EC 5.1.3.2) deficiency consistently resulted in the appearance of e imerase activity in the cultured cells. A long-term lymphoblast culture derived from one proband also contained an active epimerase enzyme. A comparison of the properties of this enzyme with those of epimerase produced by control lymphoblast lines revealed comparable Km values for UDPgalactose and NAD and identical behavior on polyacrylamide electrophoresis. However, a difference in the NAD requirement for heat stability at 400 provided some evidence for a structural defect in this enzyme. Possible explanations for the appearance of UDP-galactose 4-epimerase activity in stimulated lymphocytes include an increased rate of synthesis of a mutant enzyme and a derepression of an epimerase locus during lymphocyte transformation. The establishment of long-term lymphoblast lines from individuals with inborn errors of metabolism has proved to be a useful technique for the study of specific metabolic defects in cell culture (1, 2). These cells tend to maintain their individual genetic characteristics (3) and have a normal diploid chromosome complement. The initial intent of the present investigation was to study the effect of UDP-galactose 4-epimerase (= UDP-glucose 4-epimerase; EC 5.1.3.2) deficiency on the structure and metabolism of human lymphoblast cells in continuous culture. This enzyme defect (4), inherited as an autosomal recessive disorder (5), has been discovered in the peripheral blood cells of seven probands in three families and is characterized by elevated levels of erythrocyte galactose 1-phosphate (B. Steinmann et al., in preparation). Although there do not appear to be any associated clinical abnormalities in these individuals, deficiency of UDP-galactose 4-epimerase, which catalyzes the reaction UDP-galactose UDP-glucose, is known to result in marked abnormalities of cell wall synthesis in bacteria (6, 7) and has been postulated to be of serious consequence for mammalian cells (8).We found, however, that a lymphoblast line established from a human homozygote for this disorder contained an active epimerase enzyme which was not present in her peripheral blood lymphocytes. This called into question the role of lymphocyte transformation in the expression of epimerase activity. Therefore, we undertook further studies into the effect of the mitogen phytohemagglutinin (PHA) on the appearance of epimerase activity in deficient leukocytes and on the specific activity of epimerase in isolated normal lymphocytes. In addition, properties of the enzyme produced by the long-term lymphoblast line from a proband were com- (9) and washed in the same manner. All cultures contained 106 mononuclear cells per ml of complete medium, which consisted of RPMI 1640 supplemented with 20% fetal calf serum (GIBCO), 2 mM L-glutamine (Flow Laboratories), 100 units/ml of penicillin, 100 ,ug/ml of streptomycin...

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Section: Discussionmentioning

confidence: 99%

Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture.

Mitchell¹,

Haigis²,

Steinmann³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

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“…In mammals, IFN is classified into type-I IFN (α, β, ε, δ, τ and ω), type-II IFN (γ) and type-III IFN (λ) based on their differences in primary structure, serology and their most likely time of evolutionary divergence 8,9,10 . Interferon-gamma (IFN-γ) is a pleiotropic proinflammatory and antiviral cytokine, which was initially identified in PHA-activated mammalian lymphocyte supernatants 11 . It was demonstrated that IFN-γ is a central participant in host resistance to various infections by using IFN-γ knockout mice infected with Leishmania major 12 , Listeria monocytogenes 13 and Mycobacteria 14 .…”

Section: Introductionmentioning

confidence: 99%

Expression analysis of three immune genes Interferon-gamma, Mx and Interferon regulatory factor-1 of Japanese flounder ( Paralichthys olivaceus )

Zhang

Qiu

Liu

et al. 2017

Braz. arch. biol. technol.

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IFN-γ (Interferon-gamma), Mx and IRF-1 (Interferon regulatory factor-1) are main immune-related genes and they play important roles in the innate immune system of vertebrates. In this study, the expression level of the three immune-related genes in twelve tissues of normal adult Japanese flounder was detected using semi-quantitative RT-PCR. Thirteen time points (3h, 6h, 9h, 12h, 24h, 36h, 48h, 60h, 72h, 84h, 96h, 108h, 120h)

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“…The synthesis of interferon from lymphocytes can also be induced by immune stimulation (bacterial [16] and viral antigens [17][18][19], alloantigens [20]), anti-lymphocyte sera (21), and mitogenic lectins (22).…”

mentioning

confidence: 99%

Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Identification of the anti-viral activity as interferon and characterization of the human effector lymphocyte subpopulation.

Trinchieri¹,

Santoli²,

Dee³

et al. 1978

The Journal of Experimental Medicine

265

103

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A viral inhibitor(s) is released in the supernate of mixed cultures containing human or mouse lymphocytes and cells from certain lines. The inhibitor is active against a variety of unrelated viruses and is a protein that is not toxic for cells. It does not inactivate viruses directly, but inhibits viral replication through an intracellular mechanism that involves synthesis by the cells of both RNA and protein. These characteristics identify the inhibitor as an interferon. The anti-viral activity is contained in at least two molecular species, of approximately 25,000 and 45,000 daltons, respectively. In addition to the anti-viral activity, the supernates of the mixed cultures display an anti-cellular activity, the inhibition of DNA synthesis and of cell multiplication. The anti-viral and the anti-cellular activities are positively correlated in supernates from various cultures and in partially purified preparations. The human cell population responsible for interferon production is composed mainly of Fc-receptor positive, surface immunoglobulin negative, non-T-cell lymphocytes. The ability of certain cell lines to induce interferon seems to be preferentially associated with tumor origin or with in vitro transformation by certain viruses (Epstein-Barr virus, murine sarcoma virus).

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Interferon-Like Virus-Inhibitor Induced in Human Leukocytes by Phytohemagglutinin

Cited by 645 publications

References 11 publications

Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture.

Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture.

Expression analysis of three immune genes Interferon-gamma, Mx and Interferon regulatory factor-1 of Japanese flounder ( Paralichthys olivaceus )

Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Identification of the anti-viral activity as interferon and characterization of the human effector lymphocyte subpopulation.

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