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Title: Inhibition of natural killer cell activity by eicosapentaenoic acid in vivo and in vitro

Abstract

To examine the effects of in vivo eicosapentaenoic acid (EPA) on natural killer (NK) cell activity, C3H/He mice each received a single intraperitoneal bolus of an emulsion of trieicosapentaenoyl-glycerol (EPA-TG). Spleen cells were tested for NK activity using /sup 51/Chromium-release assays against YAC-1 target cells. Forty eight hours after injection, NK activity was inhibited in a dose-dependent manner. EPA-TG emulsion also inhibited the NK activity of NK-enriched effector cells. Decreased cytotoxicity was first noted 24 hr after injection; it resumed the baseline by 7 days. The addition of EPA-TG emulsion to a cytotoxicity assay system resulted in moderate depression of NK activity. These results demonstrate that EPA has significant immunomodulatory effects on NK activity.

Authors:
; ; ;
Publication Date:
Research Org.:
Toyama Medical and Pharmaceutical Univ., Japan
OSTI Identifier:
5471684
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochem. Biophys. Res. Commun.; (United States); Journal Volume: 150:1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; EICOSANOIC ACID; BIOCHEMICAL REACTION KINETICS; LYMPHOCYTES; CELL PROLIFERATION; CELL KILLING; CHROMIUM 51; DOSE-RESPONSE RELATIONSHIPS; EMULSIONS; IN VITRO; IN VIVO; INHIBITION; MICE; MONOCYTES; SPLEEN CELLS; TRACER TECHNIQUES; TRIGLYCERIDES; ANIMAL CELLS; ANIMALS; BETA DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CARBOXYLIC ACIDS; CHROMIUM ISOTOPES; COLLOIDS; CONNECTIVE TISSUE CELLS; DISPERSIONS; ELECTRON CAPTURE RADIOISOTOPES; ESTERS; EVEN-ODD NUCLEI; INTERMEDIATE MASS NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; LEUKOCYTES; LIPIDS; MAMMALS; MATERIALS; MONOCARBOXYLIC ACIDS; NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; RADIOISOTOPES; REACTION KINETICS; RODENTS; SOMATIC CELLS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Yamashita, N., Sugiyama, E., Hamazaki, T., and Yano, S. Inhibition of natural killer cell activity by eicosapentaenoic acid in vivo and in vitro. United States: N. p., 1988. Web. doi:10.1016/0006-291X(88)90548-7.
Yamashita, N., Sugiyama, E., Hamazaki, T., & Yano, S. Inhibition of natural killer cell activity by eicosapentaenoic acid in vivo and in vitro. United States. doi:10.1016/0006-291X(88)90548-7.
Yamashita, N., Sugiyama, E., Hamazaki, T., and Yano, S. 1988. "Inhibition of natural killer cell activity by eicosapentaenoic acid in vivo and in vitro". United States. doi:10.1016/0006-291X(88)90548-7.
@article{osti_5471684,
title = {Inhibition of natural killer cell activity by eicosapentaenoic acid in vivo and in vitro},
author = {Yamashita, N. and Sugiyama, E. and Hamazaki, T. and Yano, S.},
abstractNote = {To examine the effects of in vivo eicosapentaenoic acid (EPA) on natural killer (NK) cell activity, C3H/He mice each received a single intraperitoneal bolus of an emulsion of trieicosapentaenoyl-glycerol (EPA-TG). Spleen cells were tested for NK activity using /sup 51/Chromium-release assays against YAC-1 target cells. Forty eight hours after injection, NK activity was inhibited in a dose-dependent manner. EPA-TG emulsion also inhibited the NK activity of NK-enriched effector cells. Decreased cytotoxicity was first noted 24 hr after injection; it resumed the baseline by 7 days. The addition of EPA-TG emulsion to a cytotoxicity assay system resulted in moderate depression of NK activity. These results demonstrate that EPA has significant immunomodulatory effects on NK activity.},
doi = {10.1016/0006-291X(88)90548-7},
journal = {Biochem. Biophys. Res. Commun.; (United States)},
number = ,
volume = 150:1,
place = {United States},
year = 1988,
month = 1
}
  • In vitro exposure of human peripheral blood mononuclear cells (PBMC) to ultraviolet B (uvB) radiation has been shown to inhibit natural killer (NK) cell-mediated cytotoxicity in a dose-dependent fashion. The purpose of this study was to examine the manner by which uvB produced these deleterious effects. Inhibition of NK activity was not due to lethal injury to NK cells since the viability of cell populations enriched for NK activity was greater than 90% with the uvB doses employed. uvB appeared to directly affect NK cells since procedures which removed suppressor mechanisms, such as removal of monocytes and pharmacologic inhibition ofmore » the cyclooxygenase pathway, failed to reverse the response. Furthermore, no suppression of activity of unirradiated NK cells could be produced by coincubation of unirradiated NK cells with uv-irradiated NK cells. When the single cell assay for binding and killing was employed to determine at which stage in the lytic sequence inhibition occurred, it was found that binding was normal but lysis of bound targets and the recycling capacity of active NK cells were markedly reduced. At uvB doses above 50 J/m2, both interferon alpha (IFN-alpha) and interleukin 2 (IL-2) were ineffective in augmenting NK cell-mediated cytotoxic reactions after cells had been irradiated with uvB. Furthermore, incubation of NK cells with IFN-alpha prior to irradiation failed to protect against the inhibitory effects. These studies provide evidence that in vitro exposure of NK cells to uvB radiation inhibits their function by a direct nonlethal effect and that this inhibition occurs selectively at the postbinding stage of target cell lysis.« less
  • The in vitro cultivation of murine spleen cells with MnCl/sub 2/ resulted in the enhancement of natural killer (NK) cell activity as measured in a 4-h /sup 51/Cr-release assay. Optimal enhancement of NK activity was observed at concentrations of 10-20 ..mu..g MnCl/sub 2//culture (72-144 ..mu..M Mn/sup 2 +/). Enhancement of NK activity by MnCl/sub 2/ was not associated with any changes in the number or viability of cells following culture. The addition of antiasialo GM/sub 1/ antibody and complement to spleen cell cultures completely abrogated the enhancement of NK activity by MnCl/sub 2/. The enhancement of NK activity by MnCl/submore » 2/ in vitro was accompanied by interferon induction. The addition of rabbit antimouse interferon to spleen cells cultured with MnCl/sub 2/ reduced NK activity. NK activity in cultures treated with MnCl/sub 2/ was also reduced upon removal of plastic adherent cells. However, restoration of enhanced NK activity by addition of adherent cells to nonadherent cells in the presence of MnCl/sub 2/ was not observed. Similar effects of NK activity were observed with polyinosinic-polycytidylic acid (Poly I x C), a known interferon inducer and NK enhancer. The results demonstrate that murine splenic NK activity is enhanced in vitro by MnCl/sub 2/ and that this enhancement may be mediated by interferon induction. The results also suggest that in vitro enhancement of NK activity by MnCl/sub 2/, as with Poly I x C, may require participation of an adherent cell population for NK augmentation.« less
  • The sensitivity of human natural killer cell activity after exposure of peripheral blood mononuclear cells to different doses of gamma irradiation was examined in a group of healthy adults and several families. Theee patterns of radiation sensitivity were observed: (1) loss of all NK activity after 3000 rads irradiation; (2) loss of approximately 50% of the NK activity; and (3) maintenance of activity after this dose of irradiation. Low dose irradiation (500 to 2000 rads) resulted in an enhancement of activity. The radiation dose giving low dose activation reflected the individual's sensitivity to 3000 rads. Population studies and the segregationmore » in two informative families indicate that radiation sensitivity of NK activity is controlled by x-linked codominant genes.« less
  • During long-term dietary n-3 fatty acid supplementation, eicosapentaenoic acid (EPA) is not incorporated into phosphatidylinositol or -serine of human platelets in vivo and is not detectable in phosphatidic acid upon stimulation with thrombin. However, EPA is released from platelet phospholipids and metabolized to thromboxane B3 (TXB3). In contrast, in vitro, platelets incorporate (/sup 14/C)EPA into phosphatidylinositol, whether they contain endogenous EPA in their cellular lipids or not. Following platelet stimulation, (/sup 14/C)EPA appears in phosphatidic acid, as free fatty acid, and is transformed to TXB3. The authors conclude that the fatty acid compositions of platelet phospholipid subclasses are regulated withmore » a high degree of specificity in vivo. Qualitative differences exist between in vivo and in vitro uptake of EPA into platelet phospholipid subclasses. After in vivo incorporation, EPA is released by action of a phospholipase A2.« less
  • We studied spontaneous natural killer (NK) cell activity and radiation-resistant NK mediated cytotoxicity in four patients with clinically documented severe combined immune deficiency disease (SCID), and in one subject each with intestinal lymphangiectasia and cartilage-hair hypoplasia. We observed the preservation of spontaneous NK activity in all patients despite the presence of profound B- and T-lymphocytopenia and clinical immunodeficiency. NK activity was associated with relatively normal circulating numbers of OKM1+ lymphocytes, a population known to contain NK effectors. Spontaneous NK activity resistant to 3000 rad was increased in all patients, indicating the presence of activated natural killer cells in vivo. Themore » concept of a chronically activated immune system in these patients was further supported by the presence of increased Ia positive T cells in all subjects tested, suggesting that radioresistant NK activity may be a useful parameter to measure when assessing in vivo immune activation. Our data, as well as that of others, supports the hypothesis that at least one population of NK cells is a distinct lineage arising at the differentiation level of myeloid and lymphoid stem cells in the bone marrow.« less