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Antigenotoxic and Anticarcinogenic Effects of Styela plicata (오만둥이(Styela plicata)의 항유전독성 및 대장암 억제효과에 관한 연구)

  • Seo, Bo-Young;Kim, Jung-Mi;Lee, Seung-Cheol;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.7
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    • pp.839-845
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    • 2009
  • Colorectal cancer is the third most common malignant neoplasm in the world. Much attention has been focused on reducing colon cancer risk through medical properties of natural compound that could act as anticarcinogens. In this study, we evaluated the antioxidant and antigenotoxic effects of Styela plicata (S. plicata) from in vitro experiments. S. plicata extracts showed antioxidant activity measured by TRAP assay and antigenotoxic effect in $200{\mu}M$ $H_2O_2$ induced DNA damage in human leukocytes. Especially, freeze-dried S. plicata extracted with methanol showed the highest level of TRAP (0.225 mM) and inhibition of DNA damage (66.8%). Additionally we observed the effect of S. plicata on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) and DMH induced DNA damage (by comet assay) in male SD rats. The animals were divided into three groups and fed high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) without (normal control and DMH control) or with a 3% (w/w) of lyophilized S. plicata powder (DMH+S. plicata). One week after beginning the diets, rats were treated with DMH (30 mg/kg, s.c.) for 6 weeks except for normal control group, which was treated saline instead; dietary treatments were continued for the entire experiment. Nine weeks after DMH injection, administration of S. plicata resulted in reduction of ACF numbers, to 82.7% of the carcinogen control value ($7.67{\pm}2.04$ vs. $1.33{\pm}0.53$: p<0.01). S. plicata supplementation induced antigenotoxic effect on DMH-induced DNA damage in the blood cell (% tail intensity: $6.79{\pm}0.26$ vs. $6.13{\pm}0.22$). These data indicate that S. plicata extract has antigenotoxic and anticarcinogenic effects from in vitro experiments and S. plicata exerts a protective effect on the process of colon carcinogenesis, possibly by suppressing the DMH-induced DNA damage in blood cell and the development of preneoplastic lesions in colon.

Effects of Partial Cervus elaphus Linne' Extract on Antitumoral Immune Response in Melanoma-induced Mice (부위별(部位別) 녹용(鹿茸)이 흑색종(黑色腫) 유발(誘發) 생쥐의 종양억제(腫瘍抑制)와 면역기능(免疫機能)에 미치는 영향(影響))

  • Oh Ha-Souk;Kim Jang-Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.14 no.1
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    • pp.39-78
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    • 2000
  • Introduction: In order to investigate the effects of partial Cervus elaphus Linne' extract on antitumoral immunological, a group of mice are melanoma-induced and observed reponses in terms of the number of lymphocyte, CD4+ count, CD8+ count, CD4+/CD8+ ratio in blood and spleen, change in body weight, melanoma weight, spleen index, NK cell activity and productivity of IL-2 in each mouse Methodology: Male C57BL/6 mice were chosen as an experimental object and were divided into 5 groups randomly selection. The normal group did not receive any induction. The control group was treated with normal saline in melanoma-induced' mice. Sample I group induced the upper part of Cervus elaphus Linne' extract in melanoma-induced mice. Sample II group was induced the middle part of Cervus elaphus Linne' extract in melanoma-induced mice. Sample III group was induced the lower part of Cervus elaphus Linne' extract in melanoma-induced mice. The dosage of medication was 0.2cc daily for 14days. Results: 1. There was a significant difference in the number of lymphocyte in spleen in the sample I (upper part of Cervus elaphus Linne' extract induced) and the sample II (middle part of Cervus elaphus Linne' extract induced) compared to the control group and the sample III (lower part of Cervus elaphus Linne' extract induced). On the other hand, no significant difference was observed in the number of lymphocyte in blood in the control group and all sample groups. 2. In the CD4+ T cell ratio in blood, all three sample groups showed differences compared to the control group, though there was no significant difference between sample groups. In the CD4+ T cell ratio in spleen, there was a difference between the sample I and the control group, while the sample II and the sample III had significant difference to the control group. And also, it has been observed there were differences between the sample I and the other samples. 3. In the CD8+ T cell ratio in spleen, all three sample groups showed significant differences compared to the control group, while there was no difference between groups in the ratio in blood. 4. In the CD4+/CD8+ T cell ratio in blood, the sample I showed a significant difference compared to the control group, while the sample 1I and sample III showed differences compared to the control group. In the CD4+/CD8+ T cell ratio in spleen, all three samples showed a significant difference compared to the control group, when the sample I had a difference to the other sample groups. 5. The spleen index of the sample I and the sample II showed a significant difference compared to the sample III and the control group. In comparison between the sample groups, the sample I and the sample II showed a significant difference to the sample III. 6. In terms of the change in body weight and melanoma weight, all three sample groups showed a significant difference compared to the control group, while the comparison between the sample groups showed the sample and the sample II had a significant difference to the sample Ⅲ. 7. In comparison of NK cell activity, the sample I had a difference compared to the other groups when the effector to target cell ratio was 2.5:1. With the ratio of 5:1, the sample I and sample II showed significant differences compared to the control group, while the sample Ⅲ showed a difference. When the effector to target cell ratio was 10:1, there was no difference between groups. 8. In the productivity of IL-2, all three sample groups showed significant differences compared to the control group. In comparison between sample groups, there were significant differences between each sample groups in order of the sample I , the sample II and the sample Ⅲ. Conclusion: As one can witness from the above results, administration of partial Cervus elaphus Linne extract played important role in antitumoral immune response in melanoma-induced mice, and it could be suggested that sample I and sample II groups have prominent antitumoral immune effect.

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Effect of Tumor Hypoxia on Efficacy of Tirapazamine Combined with Fractionated Irradiation in Mouse Tumor (마우스종양에서 분할방사선조사와 병용된 Tirapazamine의 효과에 미치는 종양 저산소상태의 영향)

  • Kim, Il-Han
    • Radiation Oncology Journal
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    • v.18 no.2
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    • pp.120-126
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    • 2000
  • Purpose : Tumor hypoxia can be overcome with hypoxic cytotoxin. In mouse tumor, tirapazamine's efficacy of the potentiating radiation effect was tested by the tumor oxygenation status combined with hype facti on ated rad iotherapy .:The control and hypoxic mouse tumors we established by inoculation of RIF-1 tumor cells into the normal or previously irradiated back and thigh of C3H mice. When the tumors reached a proper size, both the control and hypoxic tumors were given hypefractionated treatments (8fractions/4 days) with saline (0.02 ml/g), tirapazamin (0.08 mM/0.02 ml/kg), irradiation (2.5 Gy), irradiation combined with tirapazamine given 30 minutes prior to each irradiation. The response was evaluated by the growth delay assay by measuring tumor size from day 0 (12 hrs prior to the first fractionation) to the day when the volume had 4-fold increase or cross sectional area had 2-fold increase. Results : Overall growth pattern showed that tirapazamine Potentiated radiation effect in back and thigh tumors grew in the normal and preirradiated tumor bed. With growth delay assay using reference point of initial tumor volume or cross sectional area, tirapazamine potentiated radiation effect 1.9 times for the control and 2.4 times for the hypoxic tumors in back, and 1.85 times for the control and 1.6 times for the hypoxic tumors. With reference of 4-fold increase of the initial volume or 2-fold increase of the cross sectional area, tirapazamine potentiated radiation effect 1.48 times for the control and 2.02 times for the hypxic tumors in back, and 1.85 times for the control and 1.6 times for the hypoxic tumors. Conclusions : Present result indicated that radiation response of hypoxic tumors was potentiated by tirapazamine in the back or thigh tumors grew in the control or preirradiated tumor bed, and potentiation of the hypoxic tumors was eDual to or greater than that of the control tumors in the back or thigh.

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Effect of Dietary Selenium on the Colon Carcinogenesis in Male ICR Mice

  • Cho, Min-Haeng;Kim, Jun-Hyeong;Hue, Jin-Joo;Kang, Bong-Su;Park, Hyun-Ji;Nam, Sang-Yoon;Yun, Young-Won;Kim, Jong-Soo;Jeong, Jae-Hwang;Lee, Beom-Jun
    • Journal of Food Hygiene and Safety
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    • v.25 no.3
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    • pp.269-277
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    • 2010
  • Selenium is an essential micronutrient for normal body function and functions as an essential constituent of selenoproteins. This study was carried out to investigate effect of selenium on the formation of colonic aberrant crypt foci (ACF) and tumor formation in a mouse model. Five-week old ICR mice were acclimated for one week and fed different selenium diet (0.02, 0.1, and 0.5 ppm) for 12 weeks. Animals received three intraperitoneal injections of azoxymethane (10 mg/kg B.W. in saline for 3 weeks), followed by 2% dextran sodium sulfate in the drinking water for a week. There were four experimental groups, including a normal control group and three different selenium levels groups. After sacrifice, the total numbers of aberrant crypt (AC) and ACF were measured in the colonic mucosa after methylene blue staining. The number of tumors was noted for tumor incidence. Liver selenium concentration was measured using ICP-AES method. Gutathione peroxidase (GPx) activity was determined using a GPx assay kit in the liver and colon. TUNEL assay and proliferating cell nuclear antigen (PCNA) staining were performed to examine the cell apoptosis and cell proliferation, respectively. Immunohistochemistry of $\beta$-catenin was also performed on the mucous membrane tissue of colon. The activity of GPx in the liver and colon was decreased in the selenium-deficient diet group while it was increased in the selenium-overloaded diet group. Apoptotic positive cells were increased in the selenium-overloaded diet group but decreased in the selenium-deficient diet group. PCNA staining area was decreased in the selenium-overloaded diet group. In addition, the $\beta$-catenin protein level in the selenium-deficient diet group was increased but decreased in the selenium-overloaded diet group. These results indicate that dietary selenium might exert a modulating effect on colon cancer by inhibiting the development of ACF and colon tumor formation in this mouse model.

Evaluation of Embolization Effect of Hepatocellular Carcinoma by Hepatic Arterial Flow Study with $^{99m}Tc$-MAA SPECT (간암에서 색전술의 효과를 평가하는데 있어서 $^{99m}Tc$-MAA SPECT를 이용한 간동맥 혈류 검사의 의의)

  • Lee, Byung-Hee;Yoo, Hyung-Sik;Lee, Jong-Doo;Chung, Jin-Ill;Park, Chang-Yun;Lee, Jong-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.1
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    • pp.62-68
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    • 1994
  • This study was aimed to compare the density of the functional microcirculation of hepatocellular carcinoma (HCC) with normal liver and to investigate the effect of hepatic-arterial oily chemoembolization (HAE) by radionuclide examination. Methods : Eight patients with HCC proven by biopsy in five, and clinically and radiologically in three were included. The mixture of 2 cc normal saline with three to four mCi of $^{99m}Tc$-MAA was infused through a hepatic-arterial catheter for a minute. Dynamic images were obtained at a rate of 4 sec per frame for a minute, and static images and SPECT were followed. Results : In three patients who underwent hepatic arterial angiography (HAA) alone, radioactivity was markedly increased in tumors compared to the adjacent liver immediately after infusion of $^{99m}Tc$-MAA. The ratios of tumoral and extratumoral up-take (T/E ratio) were above 6.5 (range; $6.5{\sim}l9$, mean; 12.5). In four of the five patients who under-went superselective HAE, T/E ratio were remark-ably decreased ($0.5{\sim}1.3$). The areas of embolization were better delineated in radionuclide study than in postembolization HAA. In the other one who was considered to be embolized completely on HAA, strong radiouptake in the tumor was disclosed (T/E ratio; 7.0). Conclusions : Therefore hepatic-arterial flow study with radionuclide imaging using $^{99m}Tc$-MAA can be a valuable method to assess the accurate embolization effect in HCC.

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The Comparison of Efficacy of Glutathione S-transeferase Placental Form Positive and Iron-Resistant Lesions in the Detection of Hepatocarcinogens (간발암성 물질 검색에 있어서 Glutathione S-transeferase Placental Form 양성 병소와 철 저항 병소의 유효성 비교 연구)

  • 강경선;김형진;이영순
    • Journal of Food Hygiene and Safety
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    • v.6 no.1
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    • pp.1-12
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    • 1991
  • Fischer 344 rats aged six weeks were diYided into four groups and group 1, 2, and 3 of rats were given an intraperitoneal injection of diethylnitrosamine at 200 mg/kg body weight and group 4 was given saline alone. Two weeks after beginning of the experiment, group 1 and 2 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for four weeks. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. During the last two weeks, group 1 and 3 of rats were received subcutaneously 3 consecutive weekly doses of iron dextran at 0.125 ml/100 g body weight. Subcutaneous injection of iron dextran resulted in hepatic siderosis in group 1 and 3 of rats. Pre neoplastic nodules were identified histopathologically by two markers, resistance to exogenous iron accumulation and glutathione S-transeferase placental form (GST-P) activity, while early carcinogen induced foci were hardly resistant to iron accumulation and though a few lesions were identified, it could hardly be distincted from normal hepatocytes of surroundings. However, GST-P positive nodules as well as foci were clearly distincted from normal hepatic cells of surroundings. In the quantitative analysis of carcinogen-induced nodules and foci, more lesions were detected by immunohistochemical method for GST-P than by prussian blue staining for resistant to iron accumulation. It is concluded that immunohistochemical marker for GST-P is more sensitive and reliable than iron-resistance marker, and that iron-resistance is not useful marker for early detection of carcinogen-induced hepatic lesions.

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Changes of Arachidonic Acid Metabolites in Silica-Exposed Alveolar Macrophage of Rats (유리규산분진에 폭로된 흰쥐의 폐포대식세포에 있어 아라키돈산 대사산물의 변화)

  • Lim, Young;Yun, Im-Goung
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.4
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    • pp.304-309
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    • 1992
  • Background: The alveolar macrophage may metabolize arachidonic acid through cyclooxygenase- and lipoxygenase- catalyzed pathways to produce a variety of metabolites of arachidonic acid. The production of these metabolites of arachidonic acid may enhance the defensive ability of the challenged lung. However, continued stimulation with the consequent production of proinflammtory metabolites of arachidonic acid, may ultimately enhance the disease process by contributing to chronic bronchoconstriction, fibrosis, and the persistent release of toxic oxygen species. Silicosis is an example of a disease process resulting from chronic exposure of the lung to foreign particles. This study was carried out to evaluate the changes of arachidonic acid metabolites from macrophages in experimental silicosis. Methods: We measured $PGE_2$, and $LTB_4$ in cultured macrophages taken from rats by radioimmunoassay at 24 and 48 hours after stimulation by silica dust, natural carbon dust, lipopolysaccharide, calcium ionophore (A23187) and medium (RPMI) as a control. For the experimental silicosis, 50 mg silica in 0.5 ml saline was administered intratracheally into the rat and grown to 20 weeks and measured $PGE_2$, and $LTB_4$ in the cultured macrophages lavaged from that rat. The used stimulants were the same as above. Results: 1) The amount of $PGE_2$ in the cultred macrophages from normal rat was significantly decreased in the group which was stimulated with silica dust for 48 hours compare with control non-stimulated group. 2) In the experimental silicosis group, $PGE_2$, release in cultured macrophages after 48 hours incubation with silica and natural carbon dust tended to be lower than those of non-stimulated group. 3) There were marked changes of $LTB_4$ in the groups of normal rats which were incubated with silica for 24, 48 hours and natural carbon for 48 hours compared with non-stimulated group. 4) In the experimental silicosis group, the release of $LTB_4$ was significantly increased macrophages cultured with silica and natural carbon dust after 24 and 48 hours incubation compared with non-stimulated group. Conclusion: The results of these studies suggest that the in vitro exposure of rat alveolar macrophge to silica and coal dust results in an alteration in alveolar macrophage metabolism of arachidonic acid that may promote an inflammatory reaction in lung tissue.

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A Study of the Capsuloligamentous Anatomy of the Glenohumeral Joint Using Magnetic Resonance Imaging and Three-Dimensional Imaging. Dynamic In Vivo Study (자기공명 영상 및 3차원 영상을 이용한 견관절 관절낭-인대의 해부학적 연구. 역동학적 생체연구)

  • Park Tae-Soo;Choi Il-Yong;Joo Kyung-Bin;Kim Sun-Il;Kim Jun-Sic;Paik Doo-Jin
    • Journal of the Korean Arthroscopy Society
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    • v.4 no.2
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    • pp.154-158
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    • 2000
  • Purpose : The purpose of this study is to demonstrate changes in the orientation ortho glenohumeral ligaments(GHL) in different degrees of abduction and rotation of the normal healthy individuals. Materials and Methods : Saline Magnetic Resonance(MR) arthrography of nine consecutive shoulders of normal healthy adults were checked. At that time, MR images were obtained in three different positions of abduction and external rotation($0^{\circ}C\;and\;0^{\circ},\;45^{\circ}C\;and\;25^{\circ}C,\;90^{\circ}$ and maximum, respectively). From a series of consecutive MRI, three-dimensional images were reconstructed after detecting the location of the middle glenohumeral ligament(MGHL) and the inferior glenohumeral ligament(IGHL) using workstation computer. Results : The shape of the MGHL was taken in double curved, and straight, and finally curved again in three different positions of the shoulder in sequence. On the other hand, the shape of the IGHL was obliquely positioned, and curvilinear, and finally straight and extended at lower part of the anterior surface of the humeral head. Conclusions : At $45^{\circ}$ of abduction and $25^{\circ}$ of external rotation, and at $90^{\circ}$ of abduction and maximal external rotation of the shoulder, the MGHL and the IGHL had the role of the most important static stabilizer of the glenohumeral joint repectively.

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Radiation Protection Effect of Blueberries in the Hematopoietic Cells of White Rats (흰쥐의 조혈세포에서 블루베리의 방사선 방호효과)

  • Lee, Jun-Haeng
    • Journal of the Korean Society of Radiology
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    • v.16 no.3
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    • pp.335-341
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    • 2022
  • The purpose of this study was to investigate the radiation protection effect of blueberries. The experimental animals used in this study were 8-week-old 21 SD male rats weighed 280-300 g. The animals were set to a normal group (A), a 5 Gy control group (B), and a 5 Gy experimental group (C) of seven rats each, and (50 mg/kg/day) of physiological saline solution of blueberries were orally administered twice a day with an oral dose of (200 mg/kg/day) for seven days and 5 Gy of radiation was irradiated in the case of groups B and C. As a result, it was identified that there was significance in white blood cells in this study (p<0.000). There was no significant difference in red blood cells or platelets. When examined in detail, among white blood cells (WBC), neutrocytes were found to be significantly different among the three groups: normal, control, and experimental groups (p<0.004). Lymphocytes were also found to be statistically significantly different among the three groups (p<0.000). Monocytes were not found to be statistically significantly different (p<0.483). When red blood cells (RBC) were examined, hemoglobin (HGB) was not found to be statistically significant different among the three groups (p<0.291). Hematocrit (HCT) was not found to be statistically significantly different among the three groups, either (p<0.564). Mean corpuscular volume (MCV) was found to be statistically significantly different among the three groups (p<0.001). Mean corpuscular hemoglobin (MCH) was also found to be statistically significantly among the three groups (p<0.028). Mean corpuscular hemoglobin concentration (MCHC) was found to be statistically significantly different among the three groups(p<0.020). Red blood cell distribution width (RDW) was not found to be statistically significantly different among the three groups (p<0.09). When platelets (PLT) were examined in detail, mean platelet volume (MpV) was found to be statistically significantly different among the three groups (MpV) (p<0.04). In conclusion, based on this study, blueberries are considered to have radiation protection effects.

The Lung Expression of Proinflammatory Cytokines, TNF-$\alpha$ and Interleukin 6, in Early Periods of Endotoxemia (내독소혈증 유발 급성폐손상에서 폐장내 Proinflammatory Cytokines 발현에 관한 고찰)

  • Moon, Seung-Hyug;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Shin-Je
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.3
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    • pp.553-564
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    • 1998
  • Background: The immediate hoot response to LPS is the production of proinflammatory cytokines that act as intercellular mediators in inflammatory reactions, including acute lung injury. These "early response" cytokines transmit signals from recognition cells to target or effector cells. This host response is further amplified by the expression of leukocyte chemoattractants, growth factors, and adhesion molecules, resulting in an array of proinflammatory events. This experiment was performed to define the lung origin of proinflammatory cytokines, such as TNF-$\alpha$, IL 6 in early periods of endotoxin induced acute lung injury (ALI). Method: The healthy male Sprague-Dawley, weighted 150 - 250g, were divided into saline control (NC) and endotoxemia-induced ALI (ETX-), and leukopenic endotoxemia-induced ALI (CPA-ETX-Group) which was induced by cyclophosphamide, 70 mg/kg i.p. injection. Acute lung injury was evoked by LPS, 5 mg/kg, intravenously administered. Bronchoalveolar lavage was performed at 0, 3, 6 h after LPS-treated to estimate the influx of phagocytes and concentration of total protein, and cytokines as TNF-$\alpha$ and IL 6 by a bioassy using MIT method. We also examined the localization of TNF-$\alpha$ and IL 6 protein in endotoxemia-challenged lung tissue by immunohistochemical stain (IH). Results: The total cell, macrophage and PMN count in BALF were elavated in ETX group compared to NC(p<0.05). In CPA-ETX group, total cell and macrophage count in BALF were not changed compared to NC. but PMN count was markedly reduced and it took part in less than 0.1 % of total BAL cells (p<0.01). The protein concentration in BALF were significantly increased in ETX and CPA-ETX group Compared to NC (p<0.05), but there was significant difference between ETX- and CPA-ETX group only at 6 h (p<0.05). This observation suggested that even if PMNs are involved in the pathogenesis of acute lung injury, their role cannot be viewed as essential The concentration of TNF-$\alpha$ and IL 6 in BALF was significantly increased in the ETX- and CPA-ETX group compared to NC. There was no difference between ETX- and CPA-ETX group. In IH, anti-TNF-$\alpha$- and anti-IL 6 antibody was strongly localized at interstitial monocytes and alveolar macrophages in endotoxemia-challenged lung tissue. From above point of view, activated alveolar macrophage/monocyte considered as a prominent source of proinflammatory cytokines in endotoxemia-challenged lung injury. Conclusion: The prominent source of proinflammatory cytokines in early periods of endotoxemia-induced lung injury will be the activated resident macrophages like an alveolar macrophage and interstitial monocytes. The pulmonary macrophage/monocyte will impact the initiation and continuance of lung injury without PMNs's certain inflammatory role, particularly in endotoxemia-induced acute lung injury.

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