간세포암 환자의 발생원인에 따른 말초혈액의 T 세포 아형과 자연살해세포능의 비교

허진욱,최바울,임현정,김수홍,김은석,윤병철,한병훈,이상욱 고신대학교 의학부 2003 高神大學校 醫學部 論文集 Vol.18 No.1

Backgrounds : Many cancer patients, such as Hepatocellular carcinoma(HCC), have a compromised cellular immune system. Several lympocytes subpopulations are involved in immunosurveillance against tumors. We try to evaluate on alteration of peripheral T cell subsets, NK cell and NK cell activity in patients with HCC. Materials and Method : Our study contain 257 patients with chronic liver disease. Of the 257 patients, 147 patients were chronic hepatitis, 44 patients were liver cirrhosis, 66 patients were Hepatocellular carcinoma. We distributed these patients to 3 groups due to cause, chronic hepatitis B (1st group, n=183), chronic hepatitis C (2nd group, n=52), alcoholic liver disease(3rd group, n=22). This study analysis ratio of CD3+, CD4+ CD8+, CD56+ T cell and NK cell activity. Results : The percentage of CD3+ and CD8+ cells were significantly decreased in LC and HCC groups. The activity of NK cells was significantly decreased in HCC than hepatitis group in HBV group. But not different in HCV and alcohol groups. NK cell and NK cell activity were significant decreased in HCC of younger patients (below 40 years) than older patients (above 60 years). Conclusions : Our study showed HCC was altered cellular immune system and decreased activity of NK cells. On the basis of this results, it can be suggested that decreased activity of NK cells according to age may be related to differnce of common age, prognosis and response of immune therapy.

간세포암 환자의 발생원인에 따른 말초혈액의 T 세포 아형과자연살해세포능의 비교

허진욱,최바울,임현정,김수홍,김은석,윤병철,한병훈,이상욱 고신대학교(의대) 고신대학교 의과대학 학술지 2003 고신대학교 의과대학 학술지 Vol.18 No.1

Backgrounds : Many cancer patients, such as Hepatocellular carcinoma(HCC), have a compromised cellular immune system. Several lympocytes subpopulations are involved in immunosurveillance against tumors. We try to evaluate on alteration of peripheral T cell subsets, NK cell and NK cell activity in patients with HCC. Materials and Method : Our study contain 257 patients with chronic liver disease. Of the 257 patients, 147 patients were chronic hepatitis, 44 patients were liver cirrhosis, 66 patients were Hepatocellular carcinoma. We distributed these patients to 3 groups due to cause, chronic hepatitis B (1st group, n=183), chronic hepatitis C (2nd group, n=52), alcoholic liver disease(3rd group, n=22). This study analysis ratio of CD3+, CD4+, CD8+, CD56+ T cell and NK cell activity. Results : The percentage of CD3+ and CD8+ cells were significantly decreased in LC and HCC groups. The activity of NK cells was significantly decreased in HCC than hepatitis group in HBV group. But not different in HCV and alcohol groups. NK cell and NK cell activity were significant decreased in HCC of younger patients (below 40 years) than older patients (above 60 years). Conclusions : Our study showed HCC was altered cellular immune system and decreased activity of NK cells. On the basis of this results, it can be suggested that decreased activity of NK cells according to age may be related to differnce of common age, prognosis and response of immune therapy.

Niclosamide Enhances NK cell Proliferation and Anti-Tumor Activity for Cancer Immunotherapy

신민화 대한의생명과학회 2023 Biomedical Science Letters Vol.29 No.4

NK (Natural killer) cells are innate immune cells and play important roles as the first immune cells to act when cancer occurs. In many cancer patients, NK cells can be seen to be inactivated, suggesting that NK cells are important in cancer treatment. In order to overcome the disadvantages of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic function of NK cells. We applied niclosamide to measure the degree of NK cell activation, and obtained unexpected results of increased NK cell numbers and anti-tumor activity. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Niclosamide is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

성인 철겹필성 빈혈 환자에서 자연 살상 세포 활성의 변화

김수홍,서정훈,김양수,어완규 고신대학교(의대) 고신대학교 의과대학 학술지 2005 고신대학교 의과대학 학술지 Vol.20 No.1

Background : Iron deficiency is the most common cause of anemia worldwide. It is well known that iron plays an important role in the metabolism of many bacterial species. A reduction in immune competence by iron deficiency or iron excess might lead to an increased susceptibility of the host to infection. Investigations have been reported of alterations in the cell-mediated immune response in iron deficient human patients. Confounding variables in clinical studies, such as additional nutritional deficiencies, pre-existing infection or other concomitant disorder, make it difficult to conclude that iron is the only causative factor in immune alteration. In this study, we investigated the change of the cell-mediated immunity in iron deficiency patients. Method : Twenty four patients with uncomplicated IDA were included in this study. The blood levels of hemoglobin, RBC indices, serum ferritin, serum iron, and TIBC were measured. The indices of cell-mediated immunity such as CD3, CD56 and NK cell activity were measured. The indices of cell-mediated immunity were compared with each hematologic mean group. The correlations between hematologic indices, iron parameters and the indices of cell mediated immunity were investigated. Results : The natural killer cell activity was significantly correlated with Hb (Spearman r=0.616, p=0.001), MCV (Spearman r=0.678, p=0.000) and MCH (Spearman r=.0721, p=0.000). But there was no significant correlations with iron, ferritin, TIBC and Iron/TIBC ratio. In Mann-Whitney test and Chi=Square test, NK cell activity was significantly associated with MCV, MCH and hemoglobin. Conclusions : There was significantly decreased natural killer cell activity in iron-deficient patients. In this study, hemoglobin, MCV and MCH are parameters of the NK cell activity in cell-mediated immunity. As a result, iron deficiency itself is a determinant of the NK cell acitivity.

성인 철결핍성 빈혈 환자에서 자연 살상 세포 활성의 변화

김수홍,서정훈,김양수,어완규 고신대학교 의학부 2005 高神大學校 醫學部 論文集 Vol.20 No.1

Background: Iron deficiency is the most common casue of anemia worldwide. It is well known that iron plays an important role in the metabolism of may bacterial species. A reduction in immune competence by iron deficiency or iron excess might lead to an increased susceptibility of the host to infection. Investigations have been reported of alterations in the cell-mediated immune response in iron deficient human patients. Confounding variables in clinical studies, such as additional nutritional deficiencies, pre-existing infection or other concomitant disorder, make it difficult to conclude that iron is the only causative factor in immune alteration. In this study, we investigated the change of the cell-mediated immunity in iron deficiency patients. Methods: Twenty four patients with uncomplicated IDA were included in this study. The blood levels of hemoglobin, RBC indices, serum ferritin, serum iron, and TIBC were measured. The indices of cell-mediated immunity such as CD3, CD56 and NK cell activity were measured. The indices of cell-mediated immunity were compared with each hematologic meal group. The correlations between hematologic indices, iron parameters and the indices of cell mediated immunity were investigated. Results: The natural killer cell activity was significantly correlated with Hb(Spearman r=0.616 p=0.001), MCV(Spearman r=0.678 p=0.000) and MCH(Spearman r=0.721 p=0.000). But there was no significant correlations with iron, ferritin, TIBC and Iron/TIBC ratio. In Mann-Whitney test and Chi-Square test, NK cell activity was significantly associated with MCV, MCH and hemoglobin. Conclusion: There was significantly decreased natural killer cell activity in iron-deficient patients. In this study, hemoglobin, MCV and MCH are parameters of the NK cell activity in cell-mediated immunity. As a result, iron deficiency itself is a determinant of the NK cell activity.

유전자 재조합 인간 성장호르몬(rhGH)이 NK 세포의 활성에 미치는 영향

강창랑,김종덕,류훈,정헌택 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.4

To evaluate the acute effect of recombinant human growth hormone(rhGH) on the activity of natural killer(NK) cell in children, we selected 6 patients of growth hormone deficient and 5 normal control children. In both groups, 0.15 IU/kg of rhGH was administered subcutaneously. The plasma growth hormone level were measured by radioimmunoassay on 0, 2, and 6 hours after administration of rhGH. To determine NK cell activity, peripheral blood mononuclear cell were separated by Ficoll-Hypaque gradient sedimentation. After this, varying concentration of viable effector cells in complete medium were added to duplicate culture of target cells(the human erythroleukemia cell line, K562) and we measured the LDH released from the cytosol into 16 hours culture medium. The average paasma level of growth hormone of growth hormone deficient and normal group were increased to the level of 41.6±23.7 and 96.3±46.5 ng/ml 2 hours after rhGH injection respectively and decreased to the level of 18.510.6 and 42.2± 5.5 ng/ ml 6 hours after rhGH injection respectively. In 16 hours_ culture medium, percent cytotoxicity of NK cell was significantly increased in the blood samples of control groups. It seemed that administration of the rhGH do not made a any effects acutely on NK cell activity in growth hormone deficient group. But in a normal control children, external administration of growth hormone increased percent cytotoxicity of NK cell activity.

족제비싸리 부위별 추출물의 항암 및 면역활성

김정화,김대호,유진현,권민철,이현정,이학주,이현용 韓國藥用作物學會 2005 한국약용작물학회지 Vol.13 No.1

족제비싸리의 각 부위별 추출물의 정상세포에 대한 독성을 살펴보기 위하여 인간 정장 폐세포인 HEL299를 이용하였으며 각 추출물은 1.0 g/l의 농도에서 최고 22.2%의 세포독성을 나타내었다. 또한 항암활성효과를 살펴보기 위하여 2가지의 암세포를 이용하였는데, A549와 AGS에서 뿌리 추출물의 경우 1.0 g/l의 농도에서 70%정도의 높은 억제활성을 나타내었고, 또한 암세포의 생육활성에 대한 정상 세포의 세포독성의 비로 나타낸 선택적 사멸도는 고농도에서는 모두 1.5이상으로 나타나 모두 암세포에 대한 선택성이 있는 것으로 나타났다. 면역세포의 생육 촉진 실험을 위하적 인간의 B cell과 T cell을 이용하였으며 각 추출물의 농도를 0.5 g/l로 하여 실험을 실시하였다. 생육도는 T cell의 경우 배양 6일째 수피 추출물이 7.5×104 cells/ml의 세포농도를 나타냈으며 B cell의 경우 배양 5일째 4.5×104 cells/ml의 농도를 나타내었다. 면역세포를 이용한 cytokine의 분비량 측정실험에서는 뿌리의 추출물이 배양시간에 따른 cytokine의 분비가 가장 높게 나타나는 것을 확인 할 수 있었다. 각 세포의 TNF-α의 분비량은 6일째 최고의 분비량을 나타내었고 뿌리추출물의 경우 대조구에 비해 7~8배 가량 정도 더 높은 분비량을 나타낸 것으로 확인되었다. IL-6의 경우 5일째까지 감소하다가 6일째부터 증가하는 경향을 나타내었는데 잎과 열매에서 가장 높은 분비량을 나타내었다. 또한 족제비싸리 추출물을 첨가한 배지에 의한 B cell과 T cell의 면역활성 및 cytokine의 분비량에 따른 NK cell의 면역 활성을 측정하였으며 모든 추출물에서 배양 시간에 따라 유의적으로 증가하는 것을 확인하였다. 그 중 족제비싸리의 수피 추출물에서 B cell의 경우 14.2×104 cells/ml, T cell의 경우 14.2×104 cells/ml으로 가장 높은 생육 활성을 나타내었다. This study was performed to experiment about useful biological activities of the parts of the extracts from Amorpha fruticosa LINNE. Experimental studies were progressed through the anticancer activities and immune activities such as cell cytotoxicity, inhibition activities of cell growth, cell growth of human B and T cell, productivity of cytokines and natural killer cell activities. The cell cytotoxicity using human Lung normal cell (HEL299) was showed cytotoxicity of below 22% by extracts of Amorpha fruticosa L. in 1.0 g/l concentration. The anticancer activities were increased in over 70% by roots extracts of Amorpha fruticosa L. in A549 and AGS cells. The immune cell growth using human immune B and T cells was increased against control by barks extracts of Amorpha fruticosa L. The secretion of cytokines (IL-6, TNF-α) from human immune B and T cells was showed secretion of the amount of cytokines by roots extracts of Amorpha fruticosa L. Also NK cell growth was increased against control all of the extracts of Amorpha fruticosa L. From the results, the roots and barks extracts of Amorpha fruticosa L. were showed useful biological activities.

Upregulation of Fas and downregulation of CD94/NKG2A inhibitory receptors on circulating natural killer cells in patients with new-onset psoriasis

Son, S.W.,Kim, E-O.,Ryu, E.S.,Kim, T-J.,Kim, J.N.,Choi, J.E.,Kye, Y.C.,Lee, K-M. Blackwell Publishing Ltd 2009 British journal of dermatology Vol.161 No.2

<P>Summary</P><P>Background </P><P>Psoriasis has been considered as a T-helper 1 cell-mediated autoimmune disease driven by collaboration with multiple components of innate and acquired immune cells. Natural killer (NK) cells have been shown to bridge innate and acquired immunity, and thus could potentially contribute to the pathophysiology of psoriasis.</P><P>Objectives </P><P>To investigate the phenotypic changes of circulating NK cells in patients with new-onset psoriasis.</P><P>Methods </P><P>Fifteen patients with plaque psoriasis (eight women and seven men) who visited our clinic after their first episode of psoriasis and did not have a history of previous systemic therapy or phototherapy participated in this study. Peripheral blood mononuclear cells were isolated and stained with a panel of antibodies against cell surface receptors expressed on T and/or NK cells and analysed by flow cytometry.</P><P>Results </P><P>As compared with normal healthy volunteers, patients with new-onset psoriasis showed no significant changes in numbers of peripheral NK, NK-T or T cells. NK activating receptors 2B4, CD48, NKG2D, CD16 and CD56 were found to be unchanged in new-onset psoriasis. However, the expression of Fas (activation-induced death receptor) was upregulated, whereas the expression of the NK inhibitory receptors CD94 and NKG2A was dramatically reduced on NK cells of new-onset psoriasis. These changes occurred at the level of mean fluorescent intensity, but minimally affected percentages of cells expressing Fas, CD94 and NKG2A.</P><P>Conclusions </P><P>Our findings demonstrate that changes in the expression of Fas and CD94/NKG2A receptors on NK cells may occur during new-onset psoriasis, and are likely to contribute to the pathogenesis of psoriasis.</P>

화살나무 및 느릅나무 추출물이 면역계세포의 활성에 미치는 영향

김종면,최민순,조정곤,정영미,박태욱,Kim, Jong-myeon,Choi, Min-soon,Cho, Jeong-gon,Jung, Young-mee,Park, Tae-wook 대한수의학회 1994 大韓獸醫學會誌 Vol.34 No.2

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.

Antitumor Activity of the Korean Mistletoe Lectin is Attributed to Activation of Macrophages and NK Cells

Yoon, Tae-Joon,Yoo, Yung-Choon,Kang, Tae-Bong,Song, Seong-Kyu,Lee, Kyung-Bok,Her, Erk,Song, Kyung-Sik,Kim, Jong-Bae The Pharmaceutical Society of Korea 2003 Archives of Pharmacal Research Vol.26 No.10

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 $\mu$ g/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity. i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.