Leukotriene D4 and indomethacine enhance additively the macrophage cytostatic activity towards MOPC-315 tumor cells

Ophir, R; Ben-Efraim, Shlomo; Bonta, I. L.

doi:10.1016/0192-0561(85)90294-2

Cited by 4 publications

(9 citation statements)

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“…These results support the concept that regulation of macrophage functions is partly under the control of lipoxygenase and cyclooxygenase metabolites of AA, in particular PGE2 and LTs. Our data also reinforce previous observations, that LTs enhance indomethacinstimulated macrophage cytostasis and natural killer cell activity [5,9], by demonstrating that inhibition of endogenous eicosanoid synthesis can modulate macrophage functions. Thus, indomethacin inhibited cyclooxygenase activity and stimulated LTB4 synthesis by macrophages incubated with A23187, and NDGA inhibited both cyclooxygenase and lipoxygenase activities.…”

Section: Discussionsupporting

confidence: 93%

“…We have confirmed an earlier report that indomethacin stimulates expression of macrophage cytostatic activity against MOPC-315 tumor cells in vitro [5]. We have further demonstrated that this effect can be inhibited by both PGE2 and NDGA.…”

Section: Discussionsupporting

confidence: 91%

“…The method used has been described in detail elsewhere [5]. Basically, 25 ~tl of the macrophage and MOPC-315 suspensions, (macrophage:tumor cell ratio of 100:1) were incubated in 96-well microtiter plates, final volume 100 l.tl.…”

Section: Methodsmentioning

confidence: 99%

“…It is possible therefore that indomethacin could stimulate macrophage functions by removing the inhibitory action of PGE2 on LT formation, so increasing the effective concentration of these proinflammatory eicosanoids. Recently Ophir et al [5] reported that mouse resident peritoneal macrophages could be activated by indomethacin in vitro to inhibit growth of MOPC-315 tumor cells. Further, macrophage cytostasis was enhanced by LTD4.…”

Section: Introductionmentioning

confidence: 99%

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Indomethacin stimulation of macrophage cytostasis against MOPC-315 tumor cells is inhibited by both prostaglandin E2 and nordihydroguaiaretic acid, a lipoxygenase inhibitor

Elliott

Tak

Pellens

et al. 1988

Cancer Immunol Immunother

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Indomethacin enhanced macrophage cytostasis against MOPC-315 tumor cells in vitro. The effect of indomethacin was inhibited by prostaglandin E2 and by the lipoxygenase inhibitor nordihydroguaiaretic acid. Prostaglandin E2 and nordihydroguaiaretic acid also inhibited indomethacin stimulation of macrophage thymidine incorporation. Indomethacin inhibited macrophage prostaglandin E2 formation and stimulated leukotriene B4 synthesis. Nordihydroguaiaretic acid inhibited leukotriene B4 production. Our data indicate that eicosanoids play a role in regulating macrophage cytostasis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Indomethacin stimulation of macrophage cytostasis against MOPC-315 tumor cells is inhibited by both prostaglandin E2 and nordihydroguaiaretic acid, a lipoxygenase inhibitor

Elliott

Tak

Pellens

et al. 1988

Cancer Immunol Immunother

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“…It was shown that PGE 2 and lipoxygenase arachidonic acid products oppose each other's actions: PGE 2 inhibits, whereas lipoxygenase products (leukotrienes) facilitate the expression of antitumor cytostatic activity. The inhibiting role of PGE 2 was supported by data showing that indomethacin (a PGE 2 inhibitor) stimulates macrophage cytostasis [11,12] and was effective in vivo as a therapeutic agent in mice bearing Ehrlich ascites tumors [13]. Conflicting results were reported by Drapier and Petit [11]: LPS treatment of murine macrophages induced cytostatic activity against syngeneic P815 mastocytoma.…”

Section: Syngeneic Tumors In Inbred Strainsmentioning

confidence: 49%

One Hundred Years of Cancer Immunotherapy: A Critical Appraisal

Ben-Efraim

1999

Tumor Biology

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First attempts of cancer immunotherapy were made approximately 100 years ago on the assumption that tumor cells are recognized as ‘foreign’ by the immune system. Later on, a whole series of experimental animal tumor models were developed. They included the use of syngeneic tumors, spontaneously arising tumors and human tumor xenografts in immunodeficient mice. The experimental data contributed to our understanding of the interaction between immunocompetent cells and their products on the one hand and tumor cells on the other. On this basis, various immunotherapeutic protocols have been devised which included the use of ‘nonspecific’ components such as bacterial adjuvants, cytokines, NK cells and macrophages and attempts were made to raise specific T and B cell responses against tumor cells. Many human tumor-associated antigens have been characterized, and various ways of increasing the immunogenicity of human tumor cells have been described. Moreover, more insight has been achieved in defining ‘high risk’ populations on the basis of genetic background, the role of environmental factors and the characterization of ‘precancerous’ cells. Some cancer vaccines have been used in clinical trials which have resulted in partially beneficial therapeutic effects but have not provided a full solution for a rational use of immunotherapy against human neoplasia.

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The effect of acute feeding of carnitine, acetyl carnitine and propionyl carnitine on basal and A23187-stimulated eicosanoid release from rat carrageenan-elicited peritoneal macrophages

1990

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Little is known about the ability of carnitine to modulate cell functions. As carnitine plays an important role in lipid metabolism we investigated the acute effect of L-carnitine, L-acetyl carnitine and L-propionyl carnithe (300 mg/kg per d; 4 d) on the basal and calcium-ionophore (A23187)-stimulated release of arachidonic acid metabolites from rat carrageenan-elicited peritoneal macrophages. A decrease in the number of peritoneal carrageenan-elicited macrophages was observed after feeding all three compounds. The basal release of prostaglandin E,, 6 keto-prostaglandin F,, and leukotriene B, was stimulated by all treatments. In contrast, thromboxane B, production was diminished by feeding carnitine and acetyl carnitine. A23187-stimulated synthesis of 6 keto-prostaglandin F,, and leukotriene B, was further enhanced by all three compounds. Acetyl carnitine and propionyl carnitine also enhanced thromboxane B, synthesis. However, no effects on prostaglandin E, formation were detected. The 6 keto-prostaglandin Flm: thromboxane B, ratio, calculated from the basal and A23187-stimulated values, was increased by carnitine treatment. In the presence of A231 87 there was also an increase in the 6 keto-prostaglandin F,,:leukotriene B, ratio. We conclude that carnitine, and possibly some of its derivatives, could modify the macrophage component of an inflammation in vivo.Carnitine compounds : Peritoneal macrophages : Arachidonic acid metabolites : Rat L-Carnitine (P-hydroxy-(y-N-trimethy1amino)-butyrate) is a natural amino acid, found particularly in animal cells, which plays an important role in fatty acid (FA) metabolism. Its major function appears to be the transport of long-chain fatty acids into mitochondria for oxidation, particularly in the heart and skeletal muscles. It has also been suggested that under abnormal metabolic conditions, e.g. diabetes, carnitine could act as a buffer for excess organic acids, so protecting mitochondria1 integrity. Its most important medical use is in treating conditions characterized by a carnitine deficiency, resulting from either a genetic defect or medical intervention, e.g. an operation or renal dialysis (Bremer, 1983). It has also been suggested that carnitine supplements may be useful in reversing Intralipid@-induced immunosuppression (De Simone et a/. 1982).Recently carnitine has been shown to modify lipid metabolism in a way which indicates that it could play a more general regulatory role than was previously thought. Specifically, carnitine has been shown to enhance the formation of arachidonic acid (AA) from linoleic acid by isolated hepatocytes (Christopherson & Norseth, 198 1). Cyclooxygenase (CO) and lipoxygenase (LO) metabolites of AA (eicosanoids) are important local modulators of inflammations. In general the CO metabolites are anti-and the LO metabolites proinflammatory, and their effects on a target cell or tissue are often opposing. For example,

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Leukotriene D4 and indomethacine enhance additively the macrophage cytostatic activity towards MOPC-315 tumor cells

Cited by 4 publications

References 0 publications

Indomethacin stimulation of macrophage cytostasis against MOPC-315 tumor cells is inhibited by both prostaglandin E2 and nordihydroguaiaretic acid, a lipoxygenase inhibitor

Indomethacin stimulation of macrophage cytostasis against MOPC-315 tumor cells is inhibited by both prostaglandin E2 and nordihydroguaiaretic acid, a lipoxygenase inhibitor

One Hundred Years of Cancer Immunotherapy: A Critical Appraisal

The effect of acute feeding of carnitine, acetyl carnitine and propionyl carnitine on basal and A23187-stimulated eicosanoid release from rat carrageenan-elicited peritoneal macrophages

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