Stimulation of lymphokine production by teleocidin, aplysiatoxin, and debromoaplysiatoxin

Yip, Y. K.; Kelker, H C; Stone-Wolff, Donna S.; Pearlstein, Kimberley T.; Urban, Carl; Vilček, Ján

doi:10.1016/0008-8749(83)90081-3

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…The results of two representative experiments with cultures of PBL derived from pooled buffy coats or a plateletpheresis residue are shown in Table I. In agreement with earlier findings (30), unseparated PBL cells stimulated with PHA or TPA alone produced low yields of IFN-gamma and LT. Combined treatment with TPA and PHA produced a synergistic enhancement in the production of both lymphokine activities which was particularly marked in total cells derived from the plateletpheresis residue.…”

Section: Inhibitory Effects Of Different Ifn Preparations In the Helasupporting

confidence: 87%

“…Earlier we observed (31) that crude IFN-gamma preparations produced by human PBL stimulated with TPA and PHA exert a greater growth-inhibiting and cytotoxic effect on HeLa cells than highly purified IFN-gamma preparations (31). In another report (30) we demonstrated that high levels of both LT and IFN-gamma activities were induced in human PBL cultures after stimulation with TPA and PHA. These observations prompted us to determine what role LT (and, possibly, some other cytotoxic proteins present in the crude IFNgamma preparations) might have in the cytotoxic activity.…”

Section: Discussionmentioning

confidence: 78%

“…We recently demonstrated that LT and IFN-gamma are induced in parallel after various forms of mitogenic stimulation (30). In another report (31), we demonstrated that crude IFN-gamma preparations produced by human peripheral blood leukocytes (PBL) upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) and phytohemagglutinin (PHA) exert a marked growth-inhibiting effect on HeLa cells and human foreskin fibroblasts (FS-4) that was not observed with more highly purified IFN-gamma preparations (31).…”

mentioning

confidence: 99%

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Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin.

Stone-Wolff¹,

Yip²,

Kelker³

et al. 1984

The Journal of Experimental Medicine

182

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Crude preparations of interferon (IFN)-gamma derived from human peripheral blood leukocyte (PBL) cultures induced with 12-O-tetra-decanoylphorbol-13-acetate (TPA) and phytohemagglutinin (PHA) were more cytotoxic to HeLa cells than partially purified nautral or highly purified recombinant human IFN-gamma preparations. Conditioned media from PBL cultures contained, in addition to IFN-gamma, a mixture of cytotoxins, including classic lymphocyte-derived lymphotoxin (LT), and a TPA-induced cytotoxic activity produced by the adherent cell population (presumably monocytes). These two types of cytotoxins, indistinguishable in the mouse L929 cell LT assay, could be differentiated by an antiserum prepared against LT derived from the B lymphoblastoid cell line RPMI 1788. This antiserum neutralized lymphocyte-derived classic LT but failed to neutralize the activity of the monocyte-derived cytotoxin. Processing of conditioned media by sequential chromatography on silicic acid, Con A-Sepharose, and DEAE-Sephacel failed to separate IFN-gamma from the LT activity. However, this procedure did remove the monocyte-derived cytotoxic activity present in the original starting material, leaving predominantly classic LT. This LT showed a slightly basic isoelectric point (pI 7.6) which partially overlapped the more basic pI range of IFN-gamma. The two lymphokine activities also could not be completely separated by fast protein liquid chromatography or molecular sieve chromatography. LT in these partially purified preparations was associated with a protein having an apparent molecular weight of 58,000 on gel filtration. This form dissociated partially into a 20,000 mol wt species after denaturation with 0.1% NaDodSO4. IFN-gamma could be selectively removed from preparations containing both IFN-gamma and LT with the aid of monoclonal antibody to IFN-gamma. The addition of purified LT to purified E. coli-derived recombinant human IFN-gamma resulted in a marked synergistic enhancement of cytotoxicity for HeLa cells.

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Section: Inhibitory Effects Of Different Ifn Preparations In the Helasupporting

confidence: 87%

Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

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Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin.

Stone-Wolff¹,

Yip²,

Kelker³

et al. 1984

The Journal of Experimental Medicine

182

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“…It differs decisively from previously identified interferon types in its antigenicity, biologic and physiochemical properties. It was produced when human peripheral leukocytes were treated with PHA plus teleocidin (the latter is a tumor promotor and used similarly to TPA in double induction protocols together with PHA [155] --see also below.…”

Section: Heterogeneity Of the Interferon Systemmentioning

confidence: 99%

“…These phorbolesters are cocarcinogens and have a multitude of effects on cellular functions often related to differentiation. How precisely TPA acts in leukocyte cultures is not established, but it is interesting to note that other tumor promotors having no structural relationship with TPA, for example the alkaloid teleocidin has a similar effect on interferon induction [155]. The studies of Marcucci and his coworkers have established additional protocols for producing high titers of IFN 7 [94].…”

Section: Superinduction Double-treatment Inductionmentioning

confidence: 99%

Interferons, a group of multiple lymphokines

Kirchner

1984

Springer Semin Immunopathol

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Burkitt's cells can be triggered by teleocidin to secrete interferon‐γ

et al. 1986

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The secretion of interferon (IFN)-gamma by T lymphocytes is mediated by the synthesis of interleukin 2 (IL-2) and the availability of IL-2 receptors. Since some Burkitt's lymphoma lines express Tac antigen and can be triggered to secrete IL-2 following activation with the new tumor promoter teleocidin, we addressed the question of whether the induction of IL-2 by B lymphocytes is accompanied by the induction of IFN-gamma. IFN-gamma has not been detected in any of the 25 cell lines studied, and following stimulation with teleocidin, we triggered the synthesis of IFN-gamma in JLP(C), a pre-Burkitt's cell line. The mechanism of IFN-gamma secretion by B lymphocytes is not clear. Our findings demonstrate that the synthesis of IL-2 by B cells is not accompanied by IFN-gamma and suggest that the synthesis of IFN-gamma is not mediated by IL-2 or IL-1 or B-cell growth factor. Neutralization studies have shown that IFN-gamma secretion is not accompanied by the induction of IFN-alpha or IFN-beta. Our data imply that B cells can be triggered to secrete IFN-gamma under certain circumstances. Whether similar function occurs in vivo is not known.

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Stimulation of lymphokine production by teleocidin, aplysiatoxin, and debromoaplysiatoxin

Cited by 8 publications

References 15 publications

Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin.

Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin.

Interferons, a group of multiple lymphokines

Burkitt's cells can be triggered by teleocidin to secrete interferon‐γ

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