Association of NKT cells and granulocytes with liver injury after reperfusion of the portal vein

Reperfusion of the liver was conducted by clamping the portal vein for 30 min in mice, followed by unclamping. Unique variation in the number of lymphocytes was induced and liver injury occurred thereafter. The major expander cells in the liver were estimated to be natural killer T cells (i.e., NKT cells), whereas conventional T cells and NK cells increased only slightly or somewhat decreased in number and proportion at that time. Reflecting the expansion of NKT cells in the liver, a Th0-type of cytokine profile was detected in sera, and cytotoxic activity was enhanced in liver lymphocytes. In NKT cell-deficient mice including CD1d (-/-) mice and athymic nude mice, the magnitude of liver injury decreased up to 50% of that of control mice. It was also suspected that accumulating granulocytes which produce superoxides might be associated with liver injury after reperfusion. This might be due to stress-associated production of catecholamines. It is known that granulocytes bear surface adrenergic receptors and that they are activated by sympathetic nerve stimulation after stress. The present results therefore suggest that liver injury after reperfusion may be mainly caused by the activation of NKT cells and granulocytes, possibly by their cytotoxicity and superoxide production, respectively.     

Leaf developmental stability of Platanus acerifolia under urban environmental stress and its implication as an environmental indicator

The developmental stability indices,leaf width based fluctuating asymmetry (FA1),and lateral vein length based directional asymmetry (RDA1) of Platanus acerifolia were studied.All the leaves were sampled from 14 sites that were categorized based on different urban environmental stress levels (UESL) in Shanghai metropolitan,China.Besides,foliar stomatal density and stomatal length were also studied as the subsidiary indices to test the availability of developmental stability indices as the indicator under a stressful environment.Results showed seasonal variation of FA1 and RDA1 existed among the 14 sites,but the data showed significant negative correlation between FA1 and UESL (FA1=0.029-0.000 9UESL+0.000 3UESL2,r=0.766 5,P=0.001 4).However,a similar trend was not found between RDA1 and UESL.Furthermore,the significant correlation among FA1 and leaf stomatal length and stomatal density implied they could be used as indicators of urban stress levels on a small scale.It seemed that RDA1 was possibly a normal parameter during leaf development but it was unavailable for use as an indicator of urban stresses.     

Fasting Enhances TRAIL-Mediated Liver Natural Killer Cell Activity via HSP70 Upregulation

Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)⁺ and CD69⁺ natural killer cells were significantly elevated (n = 7, p <0.01), as determined by flow cytometric analysis. Furthermore, we found that TRAIL⁻ natural killer cells that were adoptively transferred into Rag-2^−/− γ chain^−/− mice could convert into TRAIL⁺ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05) in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05). In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05). These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.     

富含BCAA 的PN 对肝硬化大鼠肝部分切除术后肝脏NK 的影响

目的:探讨富含支链氨基酸的肠外营养对肝硬化大鼠肝部分切除术后肝脏自然杀伤细胞(NK细胞)的影响。方法:20只肝硬化大鼠随机分为肝部分切除术后行8.5%Novamin的肠外营养5 d组10只,肝部分切除术后行10%Hepa的肠外营养5 d组10只。应用流式细胞仪测定大鼠肝脏NK细胞的百分率;应用4小时51Cr释放法测定肝脏NK细胞的杀伤活性。结果:与8.5%Novamin的肠外营养5 d组比较,10%Hepa的肠外营养5 d组肝脏NK细胞占全部淋巴细胞的百分比和肝脏NK细胞杀伤活性明显升高(P<0.05)。结论:富含支链氨基酸的肠外营养可以增加肝脏NK细胞的百分率和肝脏NK细胞的杀伤活性。     

城市胁迫生境下二球悬铃木叶片的发育稳定度及其环境指示功能

对采自上海市区14个样点的二球悬铃木叶片发育稳定度、叶片气孔密度和气孔长径进行研究。结果表明,在3个采样时期,根据叶片宽度确定的非稳态不对称指数(FA1)和根据叶片侧脉长度确定的偏向性不对称指数(RDA1)在不同环境胁迫程度(UESL)下均表现出显著的差异,但进一步分析表明,各样点FA1与环境胁迫程度UESL之间呈显著的非线性回归关系,而RDA1与环境胁迫程度之间却未显示类似关系。此外,FA1与叶片气孔密度和气孔长径之间的显著相关关系表明,它们可共同作为指示小尺度上环境胁迫的有效指标,而RDA1是叶片的一种正常发育状态参数,并不适于反映环境胁迫状态。     

Unimpaired ability to generate adherent lymphokine-activated killer (A-LAK) cells in patients with primary or metastatic liver tumors

Summary Adherent lymphokine-activated killer cells (A-LAK cells) obtained from human peripheral blood mononuclear cells represent a population of potent antitumor effectors enriched in interleukin-2(IL-2)-activated natural killer cells. This study shows that A-LAK cells can be successfully generated from the blood of patients with liver cancer not treated with adjuvant chemotherapy or irradiation. Mononuclear cells were isolated from the blood of 33 patients with liver tumors (6 benign, 10 primary malignant, 17 metastatic) at the time of liver resection. A-LAK cells were separated by adherence to plastic following activation of peripheral blood mononuclear cells in 1000 U/ml recombinant IL-2. A-LAK cells (enriched up to 92% in CD3^–CD56⁺ cells) showed better subsequent expansion and two to six times higher antitumor cytotoxicity per cell than unseparated LAK cells cultured under the same conditions. The ability to generate A-LAK cells with superior in vitro cytotoxicity from the blood of most patients with liver cancer indicates that adoptive cellular immunotherapy may be a feasible and new way of treatment for primary and secondary hepatic neoplasms in man.     

Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells in vitro, but its physiological role in tumor surveillance remains unknown. Here, we report that TRAIL is constitutively expressed on murine natural killer (NK) cells in the liver and plays a substantial role in suppressing tumor metastasis. Freshly isolated NK cells, but not natural killer T cells or ordinary T cells, from the liver expressed cell surface TRAIL, which was responsible for spontaneous cytotoxicity against TRAIL-sensitive tumor cells in vitro along with perforin and Fas ligand (FasL). Administration of neutralizing monoclonal antibody against TRAIL significantly increased experimental liver metastases of several TRAIL-sensitive tumor cell lines. Such an anti-metastatic effect of TRAIL was not observed in NK cell-depleted mice or interferon-gamma-deficient mice, the latter of which lacked TRAIL on liver NK cells. These findings provide the first evidence for the physiological function of TRAIL as a tumor suppressor.     

The administration of naked plasmid DNA into the liver induces antitumor innate immunity in a murine liver metastasis model

BACKGROUND: Gene therapy is a promising strategy against advanced cancer; however, the safety of viral vectors and the effectiveness of non-viral vectors have not yet been established. Recently, a hydrodynamics-based procedure was reported to be an effective and safe method to deliver and transduce DNA into the liver. Herein, we propose a strategy for liver metastasis by a hydrodynamics-based procedure to deliver naked non-coding plasmid DNA (pDNA) into the liver as an immunocompetent organ. METHODS AND RESULTS: Mice received a rapid intravenous (i.v.) injection of naked pDNA in a large volume of saline (0.1 ml/g body weight). The single administration of a naked non-coding pDNA by the hydrodynamics-based procedure before tumor cell inoculation strongly suppressed liver metastasis formation. However, the usual i.v. injection (200 microl/body) of the same dose of naked pDNA could not suppress liver metastasis formation. Following the methylation of CpG sequences within the pDNA using CpG methylase, injection of the methylated pDNA by the hydrodynamics-based procedure could not suppress liver metastasis formation. Gadolinium chloride pretreatment did not interfere with this antitumor effect, but anti-asialo GM1 antiserum treatment did. These findings indicated that natural killer (NK) cells, not Kupffer cells, were involved in this antitumor effect. The NK cytotoxic activities of liver mononuclear cells were strongly enhanced after receiving a naked pDNA by the hydrodynamics-based procedure. CONCLUSIONS: These observations suggest that unmethylated CpG motifs in pDNA stimulated immune cells, resulting in the activation of NK cells in the liver to suppress liver metastases in a murine model.     

Identification of effector cells for TNFalpha-mediated cytotoxicity against WEHI164S cells

WEHI164S cells were found to be very sensitive targets for in vitro killing in a 6-h culture when liver or splenic lymphocytes were used as effector cells in mice. Of particular interest, a limiting cell-dilution analysis showed that effector cells were present in the liver with a high frequency (1/4,300). In contrast to YAC-1 cells as NK targets, perforin-based cytotoxicity was not highly associated with WEHI164S killing. The major killer mechanism for WEHI164S targets was TNFalpha-mediated cytotoxicity. By cell sorting experiments, both NK cells and intermediate T cells (i.e., TCR(int) cells) were found to contain effector cells against WEHI164S cells. However, the killer mechanisms underlying these effector cells were different. Namely, NK cells killed WEHI164S cells by perforin-based cytotoxicity, TNFalpha-mediated cytotoxicity, Fas ligand cytotoxicity, and other mechanisms, whereas intermediate T cells did so mainly by TNFalpha-mediated cytotoxicity. These results suggest that TNFalpha-mediated cytotoxicity mediated by so-called natural cytotoxic (NC) cells comprised events which were performed by both NK and intermediate T cells using somewhat different killer mechanisms. Intermediate T cells which were present in the liver were able to produce TNFalpha if there was appropriate stimulation.     

Sensitization of mouse splenocytes to normal tissue antigens and natural killer activity. I. The effect of immunization with normal syngeneic tissues

Immunization of C3HA mice with homogenized syngeneous liver led to sensibilization of splenocytes towards liver antigens and to the increase in natural killer cell activity towards K-562 cells. The dynamics of sensibilization and cytotoxicity in different time intervals after immunization has led to a conclusion about a correlation between the two above phenomena.     

Activation of maternal killer cells in the pregnant uterus with chronic indomethacin therapy, IL-2 therapy, or a combination therapy is associated with embryonic demise

We have previously shown that NK lineage cells migrate to the murine decidua of pregnancy; but with advancing gestation, they are progressively inactivated in situ by prostaglandins of the E series (PGE2) secreted by decidual cells and decidual macrophages. We have also shown that the same mechanism inactivates all killer lineage cells in the human decidua, and that this inactivation is at least in part due to a down-regulation of IL-2 receptors and an inhibition of IL-2 production in situ. We examined whether chronic indomethacin therapy (to block prostaglandin synthesis), or a systemic administration of a high dose of IL-2, or a combination of both agents administered to pregnant mice could activate killer cells in situ and interfere with the progress of pregnancy; and if so, whether there was a causal relationship between the two events. Pregnant CD1 mice (Day 5 of gestation) were subjected to chronic indomethacin therapy (14 micrograms/ml in drinking water up to Day 15, or 50 micrograms twice daily sc or ip up to Day 10), high dose IL-2 therapy (25,000 Cetus U of human recombinant IL-2, ip every 8 or 12 hr for 3-5 days), or a combination of the two. These treatments led to pregnancy loss in 89-100% of mice, in contrast to 1% loss in control, vehicle-treated mice. Uterine mononuclear cells isolated from the embryo resorption sites exhibited high killer activity against YAC-1 lymphoma as well as murine trophoblast targets, with NK-like phenotype (Asialo GM-1+, Thy-1-) after indomethacin therapy and LAK-like phenotype (AGM-1+, Thy-1+) after IL-2 or indomethacin + IL-2 therapy. That AGM-1+ killer cells resulted in the pregnancy loss was suggested by the findings that in two of three separate experiments, iv injections of AGM-1 ab into pregnant indomethacin + IL-2-treated mice nearly completely prevented the fetoplacental demise (reducing it to 7.7% from 100%). These results reveal that PGE2-mediated inactivation of killer lineage cells in the decidua in situ is conducive to the survival of the conceptus.     

自然杀伤细胞参与肝脏恶性肿瘤免疫逃逸研究进展

自然杀伤细胞是机体固有免疫系统重要组成部分,在肝脏等免疫器官中含量丰富,而且免疫表型、功能等表现出器官特异性。在正常情况下,靶细胞表面的配体与自然杀伤细胞表面的活化性受体直接结合并释放细胞毒性物质,诱导活化靶细胞凋亡程序,从而发挥抗感染、抗肿瘤作用。然而肿瘤细胞仍能够通过多种途径逃逸机体的免疫监视功能,研究认为肿瘤细胞抗原异常表达、肿瘤微环境中细胞因子及其他免疫细胞相互作用等因素所引起的自然杀伤细胞活性降低对于诱导肿瘤免疫逃逸起重要作用。本文综述了自然杀伤细胞在肝脏恶性肿瘤发生过程中参与免疫逃逸的机制及研究进展,以期为临床抗肿瘤免疫治疗的研究提供参考。     

Natural killer and natural killer T cells in liver fibrosis

The liver lymphocyte population is enriched with natural killer (NK) cells, which play a key role in host defense against viral infection and tumor transformation. Recent evidence from animal models suggests that NK cells also play an important role in inhibiting liver fibrosis by selectively killing early or senescence activated hepatic stellate cells (HSCs) and by producing the anti-fibrotic cytokine IFN-γ. Furthermore, clinical studies have revealed that human NK cells can kill primary human HSCs and that the ability of NK cells from HCV patients to kill HSCs is enhanced and correlates inversely with the stages of liver fibrosis. IFN-α treatment enhances, while other factors (e.g., alcohol, TGF-β) attenuate, the cytotoxicity of NK cells against HSCs, thereby differentially regulating liver fibrogenesis. In addition, the mouse liver lymphocyte population is also enriched for natural killer T (NKT) cells, whereas human liver lymphocytes have a much lower percentage of NKT cells. Many studies suggest that NKT cells promote liver fibrogenesis by producing pro-fibrotic cytokines such as IL-4, IL-13, hedgehog ligands, and osteopontin; however, NKT cells may also attenuate liver fibrosis under certain conditions by killing HSCs and by producing IFN-γ. Finally, the potential for NK and NKT cells to be used as therapeutic targets for anti-fibrotic therapy is discussed. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.     

Natural killer cell activity in mice infected with Acanthamoeba culbertsoni]

The natural killer cell activity of splenocytes and TBC, active NK cells, recycling capacity of natural killer cells were observed by means of both the 51Cr-release cytotoxicity assay and single cell cytotoxicity assay against YAC-1. C3H/HeJ mice were infected intranasally with 1 x 10(4) or 1 x 10(5) trophozoites of pathogenic Acanthamoeba culbertsoni. The infected mice showed mortality rate of 34% in 1 x 10(4) group and 65% in 1 x 10(5) group, and mean survival time was 16.40 +/- 3.50 and 13.20 +/- 4.09 days respectively. The cytotoxic activity of natural killer cells of the 2 groups was significantly higher than that of non-infected mice from the 12th hour to the 2nd day after infection, showing the highest on the first day. On the 10th day after infection, the cytotoxic activity of natural killer cells was significantly suppressed as compared with that of the control. There was no significant difference in NK cell cytotoxicity between two infected groups. The target-binding capacity and active NK cells of natural killer cells in 1 x 10(5) trophozoite infected mice was significantly increased on the 12th hour and the first day after infection as compared with the control group. Maximal recycling capacity (MRC) was not changed during the observation period. The present results indicated that the elevation of natural killer cell activity in the mice infected with A. culbertsoni was due to elevation of target-binding capacity and increased active NK cells of natural killer cells, and not due to the maximal recycling capacity of the individual NK cell, and there was no difference between two experimental dose groups.     

Leaf developmental stability of Platanus acerifolia under urban environmental stress and its implication as an environmental indicator

The developmental stability indices, leaf width based fluctuating asymmetry (FA1), and lateral vein length based directional asymmetry (RDA1) of Platanus acerifolia were studied. All the leaves were sampled from 14 sites that were categorized based on different urban environmental stress levels (UESL) in Shanghai metropolitan, China. Besides, foliar stomatal density and stomatal length were also studied as the subsidiary indices to test the availability of developmental stability indices as the indicator under a stressful environment. Results showed seasonal variation of FA1 and RDA1 existed among the 14 sites, but the data showed significant negative correlation between FA1 and UESL (FA1 = 0.029 − 0.000 9UESL + 0.000 3UESL², r = 0.766 5, P = 0.001 4). However, a similar trend was not found between RDA1 and UESL. Furthermore, the significant correlation among FA1 and leaf stomatal length and stomatal density implied they could be used as indicators of urban stress levels on a small scale. It seemed that RDA1 was possibly a normal parameter during leaf development but it was unavailable for use as an indicator of urban stresses. __________ Translated from Chinese Journal of Ecology, 2005, 24(7): 719–723 [译自: 生态学杂志, 2005, 24(7): 719–723]     

Autologous tumor cell killing activity of tumor-associated lymphocytes in patients with head and neck carcinomas

In order to select the most cytotoxic effector cells for adoptive immunotherapy, lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TILs) and autologous mixed lymphocyte tumor cell culture (MLTC) cells derived from peripheral blood mononuclear cells (PBMC) in the same subject with head and neck carcinomas were prepared. The autologous tumor cell killing activity and cell surface phenotypes of each of the three effector cells were studied. MLTC cells cultured with interleukin-2 (IL-2) showed the strongest cytotoxic activity among these three different effector cells. Although TILs had suppressed killing activity immediately after isolation, after successive cultivations with IL-2, a cytotoxic activity against autologous tumor cells stronger than that of LAK cells appeared. Both IL-2 stimulated MLTC cells and TILs showed an enrichment of CD8 positive and CDU negative cells in a CD3 positive subpopulation.Abbreviations CD cluster differentiation - IL-2 interleukin-2 - LA lymphokine activated - LAK lymphokine activated killer - MLTC mixed lymphocyte tumor cell culture - NK natural killer - PBMC peripheral blood mononuclear cells - TILs tumor infiltrating lymphocytes     

Leu-Leu-OMe sensitivity of human activated killer cells: delineation of a distinct class of cytotoxic T lymphocytes capable of lysing tumor targets

Sensitivity to L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) was used to characterize the phenotype of human activated killer cells. Natural killer cells (NK) and the precursors of both the alloantigen-specific cytotoxic T lymphocytes (CTL) and the NK-like activated killer cells generated after stimulation with allogeneic cells were deleted from human peripheral blood lymphocytes by preincubation with Leu-Leu-OMe. It was noted, however, that cytotoxic lymphocytes could be generated from Leu-Leu-OMe-treated lymphocyte precursors after 2 to 6 days of culture with the nonspecific mitogen, phytohemagglutinin (PHA). The characteristics of these killer cells indicated that they were a unique population that could be distinguished from other cytotoxic cells. Killing by these cells exhibited slow kinetics in that 18 hr cytotoxicity assays were required to detect full cytotoxic potential. When 18 hr assays were used, PHA-stimulated cytotoxic cells generated from Leu-Leu-OMe-treated lymphocytes were able to kill both NK-sensitive K562 cells and the relatively NK-resistant renal cell carcinoma cell line, Cur. These cytotoxic lymphocytes were HNK-1, Leu-11b (CD16), and OKM1 (CR3)-negative at both the precursor and effector stage of activation. Furthermore, these cells were derived from a CD3-positive precursor. Finally, killing by activated effectors was inhibited by OKT3. Unlike activation of Leu-Leu-OMe-sensitive large granular lymphocytes, generation of these cytotoxic T cells was totally prevented by treatment with mitomycin c before stimulation. Thus, a unique class of tumoricidal T cells can be characterized by resistance of lymphocyte precursors to a concentration of Leu-Leu-OMe, which has been shown to ablate NK, mixed lymphocyte culture-activated NK-like cytotoxic precursors, and the precursors of alloantigen-specific CTL.     

Natural killer (NK) and lymphokine-activated killer (LAK) cell functions from healthy dogs and 29 dogs with a variety of spontaneous neoplasms

To investigate natural killer (NK) and lymphokine-activated killer (LAK) cell functions from 10 healthy dogs and 29 dogs with a variety of spontaneous neoplasms, large granular lymphocytes (LGLs) from blood samples were separated by a 58.5% Percoll density gradient. LGLs were stimulated with a low dose of recombinant human interleukin 2 (rhIL-2) for 7 days. Cytotoxicity of effector cells against the susceptible CTAC cell line was measured before and after stimulation. Compared with those before stimulation, the percentage of LGLs after stimulation with rhIL-2 was found to be significantly increased (P<0.01) in both dogs with tumors and controls. However, the increase was significantly higher in control animals, indicating a defect in proliferation ability of NK cells in canine tumor patients. After stimulation with rhIL-2, lymphokine-activated killer (LAK) cell activity in dogs with tumors was significantly lower (P<0.01) when compared with controls. Reduced cytotoxicity of rhIL-2–activated NK cells in dogs with tumors seems to be attributable to the presence of a diminished proliferative capacity of NK cells and a decreased ability of LAK cells to lyse target cells. Further knowledge of the precise function of IL-2–activated NK cells in dogs with tumors may help to optimize new and therapeutically beneficial treatment strategies in canine and human cancer patients. Our findings suggest that the dog could also serve as a relevant large animal model for cancer immunotherapy with IL-2.     

Fate of intravenously administered rat lymphokine-activated killer cells labeled with different markers

Summary Rat lymphokine-activated killer (LAK) cells, generated by adhering rat splenocytes isolated from the 52% Percoll density fraction to plastic flasks, demonstrate restricted in vivo tissue distribution, localizing in the lungs and liver after 2 h, but redistributing into the liver and spleen 24 h after i.v. administration. However, a different pattern of distribution was observed when this population of LAK cells was labeled with one of four commonly used radioisotopes. For example, LAK cells showed a high distribution into the lungs 30 min after administration when labeled with⁵¹Cr,¹²⁵I-dUrd or¹¹¹In-oxine, whereas¹¹¹InCl-labeled LAK cells showed an equal distribution into the blood, lungs and liver at this time. Two hours after administration, cells labeled with¹¹¹In-oxine showed an equivalent distribution into the lungs and liver, those labeled with¹²⁵I-dUrd or⁵¹Cr showed a high accumulation in the lungs, whereas those labeled with¹¹¹In-Cl entered more into the liver and blood. The pattern of distribution of¹¹¹In-Cl- or¹¹¹In-oxine-labeled cells was confirmed using gamma camera imaging analysis. By 24 h, LAK cells labeled with¹¹¹InCl,¹¹¹In-oxine or⁵¹Cr distributed in the liver and spleen in variable concentrations. In contrast, cells labeled with¹²⁵I-dUrd were not detected in any organ tested.This study was paralleled by monitoring the distribution of LAK cells labeled with Hoechst 33342 (H33342) and analyzed for the presence of fluoresceinated cells in different organs either by flow cytometry analysis, or in frozen section. The data indicate that the distribution pattern of LAK cells labeled with¹¹¹In-oxine is the closest to the distribution of H33342-labeled cells. Of all the radioisotopes used,¹²⁵I-dUrd has the most disadvantages and is not recommended for monitoring the in vivo distribution of leukocytes.     

Secretion of prostaglandin type E (PGE) by tumor cells of Syrian hamsters in in vitro contact with natural killers

The ability of Syrian hamster tumor cells of the same origin but with different degrees of malignancy to secrete prostaglandin E (PGE) was studied following their in vitro contact with Syrian hamster natural killer cells (NK cells). Syrian hamster NK cells were shown to lose significantly cytotoxic activity after their contact with malignant tumor cells. Short-term in vitro contact of malignant tumor cells with human and Syrian hamster NK cells resulted in a rapid PGE secretion into the culturing medium. PGE was determined in the culturing medium, using the biological test, described in the paper, or direct radioimmunoassay. No PGE secretion was observed after the treatment of tumor cells with indomethacin. It is assumed that PGE secretion by malignant tumor cells is one of the mechanisms of their protection against natural killer cells.