AUGMENTATION OF MURINE NATURAL-KILLER CELL-ACTIVITY BY SWAINSONINE, A NEW ANTIMETASTATIC IMMUNOMODULATOR
- 15 March 1988
- journal article
- research article
- Vol. 48 (6), 1410-1415
Abstract
Swainsonine, an indolizidine alkaloid, has been found to inhibit the experimental metastasis of B16-F10 melanoma cells when administered systemically to syngeneic C57BL/6 mice. The inhibition was both potent and dose dependent with .gtoreq. 80% reduction in pulmonary colonization being observed after only 24-h exposure to 3 .mu.g/ml of swainsonine in drinking water. In contrast, the inhibitory activity of swainsonine was completely abrogated when assays were performed in mice depleted of their natural killer (NK) cell activity either experimentally (anti-asialo-GM1 antibody- or cyclophosphamide-treated C57BL/6 mice) or as a result of genetic mutation (homozygous C57BL/6bg/bg beige mice). Swainsonine elicited a 32.0% increase in spleen cell number 2 days after administration and induced a concomitant 2- 3-fold increase in splenic NK cell activity. These results indicate (a) an absolute requirement for a functional NK cell population in order for swainsonine to exert its inhibitory effects on experimental metastasis, and (b) that the antimetastatic activity of swainsonine is mediated primarily through the ability of the drug to augment NK cell reactivity. On the basis of these findings, swainsonine can be classified as a new immunomodulator that has the ability, at least in a prophylactic setting, to block tumor metastasis.This publication has 34 references indexed in Scilit:
- Identification of ganglio-N-tetraosylceramide as a new cell surface marker for murine natural killer (NK) cells.The Journal of Immunology, 1980
- The effect of immunopharmacological agents on mouse natural cell-mediated cytotoxicity and on its augmentation by poly I:CImmunopharmacology, 1979
- BEIGE MUTATION IN THE MOUSE .1. STEM-CELL PREDETERMINED IMPAIRMENT IN NATURAL KILLER CELL-FUNCTION1979
- BEIGE MUTATION IN THE MOUSE .2. SELECTIVITY OF THE NATURAL KILLER (NK) CELL DEFECT1979
- Augmentation of Mouse Natural Killer Cell Activity by Interferon and Interferon InducersThe Journal of Immunology, 1979
- Effect of Chemotherapeutic Agents on Natural Cell-Mediated Cytotoxicity in Mice2JNCI Journal of the National Cancer Institute, 1978
- LYSOSOMAL STORAGE IN SWAINSONA SPP. TOXICOSIS: AN INDUCED MANNOSIDOSISNeuropathology and Applied Neurobiology, 1978
- Natural cell‐mediated cytotoxicity in rats. III. Effects of immunopharmacologic treatments on natural reactivity and on reactivity augmented by polyinosinic‐polycytidylic acidInternational Journal of Cancer, 1978
- Augmentation of natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic target cellsInternational Journal of Cancer, 1977
- EFFECT OF CYCLOPHOSPHAMIDE AND OTHER DRUGS ON INCIDENCE OF PULMONARY METASTASES IN MICE1977