Biological characterization of guinea pig lymphotoxin production

Rundell, John O.; Evans, Charles H.

doi:10.1016/0162-3109(79)90016-x

Cited by 12 publications

(5 citation statements)

References 13 publications

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“…The lymphotoxin is a lymphokine with a high molecular weight [7], but we found the strongest releasing activity in fractions of a m.w. range smaller than 12,500 daltons.…”

Section: Discussionmentioning

confidence: 92%

5-Hydroxytryptamine releasing activity in culture supernatants of guinea pig lymphocytes

1984

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5-Hydroxytryptamine (5-HT) is not only involved in anaphylactic reactions but also in delayed-type hypersensitivity (DTH) reactions. Supernatants of cultivated guinea pig spleen lymphocytes were investigated for possessing 5-HT releasing activity. Both fractionated supernatants of mixed lymphocytes unspecifically stimulated by Concanavalin A (Con A) and fractionated supernatants of non-stimulated mixed lymphocytes decrease the 5-HT content of rabbit thrombocytes. Fractions of a molecular weight smaller than 12,500 daltons are more effective than fractions of a higher molecular weight range. The 5-HT releasing activity of the supernatants is discussed in comparison to a cell migration stimulating activity.

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“…The lymphotoxin is a lymphokine with a high molecular weight [7], but we found the strongest releasing activity in fractions of a m.w. range smaller than 12,500 daltons.…”

Section: Discussionmentioning

confidence: 92%

5-Hydroxytryptamine releasing activity in culture supernatants of guinea pig lymphocytes

1984

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“…While the growth-inhibitory and anticarcinogenic activities ascribed to lymphotoxin were initially observed with predominantly nonfractionated, dialyzed, or diafiltered lymphokine preparations [8,10,34,52], the activities are continually being confirmed in investigations in which more highly purified lymphotoxins are used [4,9,63]. Lymphotoxin can be produced by mitogen or antigen stimulation of leukocytes for periods ranging from 4 -8 h [23,46] to 5 -7 days [22]. In our laboratory lymphotoxin is generated by the culture of 10 7 lymphoid cells from lymph nodes, peripheral blood, spleen, or other leukocyte populations from humans or experimental animals for a period of 24 h in serum-free medium with antigen or mitogen to activate the cells [9].…”

Section: Summary L Ymphotoxin a Glycoprotein Lymphokine Possesses mentioning

confidence: 99%

Lymphotoxin ? An immunologic hormone with anticarcinogenic and antitumor activity

Evans

1982

Cancer Immunol Immunother

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“…Guineapig lymphotoxin purified in this manner is predominantly beta-lymphotoxin with a MW approximating 45,000 (Ransom et al, 1982b). It is free of detectable interferon (Rundell and Evans, 1981), does not activate NK cells (Ransom and Evans, 1982), an activity attributed to interferon (Herberman et al, 1979) and to interleukin-2 (Henney et al, 1981), and is outside the range of isoelectric PH'S (PH 3 and 6) of guinea-pig macrophage migration inhibitory factor (MIF) (Remold et al, 1981), thus excluding the presence of MIF.…”

Section: Lymphotoxinmentioning

confidence: 99%

“…Lymphotoxin is an immunologic hormone with several anticancer actions (Evans, 1982). Lymphotoxin is preferentially cytotoxic via cytolytic or cytostatic mechanisms for malignant cells (Rundell and Evans, 1981;Evans and Heinbaugh, 1982), is anticarcinogenic in vitro (Evans and DiPaolo, 1981) and in vivo (Ransom et al, 1982a), and enhances the susceptibility of preneoplastic and malignant cells to natural killer (NK)-cell-mediated cytotoxicity in vitro (Ransom and Evans, 1982;Evans, 1983). Enhancement of NK cell cytotoxicity is restricted to cells susceptible to the cytostatic action of lymphotoxin, i.e., normal cells are unaffected.…”

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confidence: 99%

Lymphotoxin amplification of tumor growth inhibition is specific for natural killer cells but not for macrophages

Ransom

Pintus

Evans

1983

Intl Journal of Cancer

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Lymphotoxin augments the susceptibility of tumorigenic guinea-pig cells to natural killer (NK) cell cytolysis in vitro but does not directly stimulate either NK cell or macrophage cytolytic action. The question whether lymphotoxin enhances the susceptibility of tumorigenic guinea-pig cells to cytolysis or other means of growth inhibition in vivo by syngeneic NK cells or macrophages was, therefore, examined using a modified tumor cell neutralization (Winn) assay. Mineral oil-, thioglycollate- or casein-induced peritoneal leukocytes, but not the macrophages isolated from the elicited leukocytes obtained from nonimmunized strain 2/N guinea-pigs, effected enhanced cytolysis of lymphotoxin-treated guinea-pig benzo (a)pyrene-induced 104CI tumor cells in vitro. Neither guinea-pig splenic NK cells nor oil-induced peritoneal macrophages alone inhibited the growth of 104CI cells as tumors in vivo when admixed with 104CI cells and injected into guinea-pigs. However, when the 104CI cells were treated with lymphotoxin before addition of effector cells, NK cells but not macrophages significantly reduced tumor growth in vivo. Therefore, the ability of lymphotoxin to increase the sensitivity of tumor cells to destruction mediated by natural leukocytes is specific for NK cells as compared to macrophages. This form of lymphokine amplification of natural leukocyte cytotoxicity may be one mechanism by which natural and acquired immunity serves or fails to prevent cancer and should be an important consideration in therapeutic approaches to eradicate or control tumor growth.

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Biological characterization of guinea pig lymphotoxin production

Cited by 12 publications

References 13 publications

5-Hydroxytryptamine releasing activity in culture supernatants of guinea pig lymphocytes

5-Hydroxytryptamine releasing activity in culture supernatants of guinea pig lymphocytes

Lymphotoxin ? An immunologic hormone with anticarcinogenic and antitumor activity

Lymphotoxin amplification of tumor growth inhibition is specific for natural killer cells but not for macrophages

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