골수유핵세포의 경내피세포 및 경기질세포 이행 과정에서 류코트리엔 B_(4) 역할과 활성산소종 억제의 영향

문영철,오수아,유은선,최문영,안지영,성주명 이화여자대학교 의과학연구소 2008 EMJ (Ewha medical journal) Vol.31 No.2

Objectives:Leukotriene B_(4)(LTB4) is lipid mediator derived from membrane phospholipids during the process of inflammation, having many roles(ie;inducer of chemotaxis, the production of nitric oxide, transepithelial migration of neutrophil). The major activities of LTB4 include the recruitment and activation of leukocytes, suggesting that it may involve the process for transendothelial migration of nuclear cells in bone marrow environment. Reactive Oxygen Species (ROS) have a cell signaling roles that are involved in signal transduction cascades of numerous growth factor-, cytokine-, and hormone-mediated pathways, and regulate many biological systems. In this present study, we focused on the role of LTB4 and ROS on transmigration of bone marrow nuclear cells across endothelial or stromal cell monolayer. Methods:MS-5, murine stromal cell line cells, or bEnd.3, murine microvascular cell line cells, were grown to confluence on microporous transwell membrane. Murine marrow cells were placed on top of the prepared transwell membrane. The transwells were then seated in wells containing media and LTB4 with or without pretreatment of N-acetylcysteine(NAC), an oxygen free radical scavenger, or diphenylene iodonium(DPI), an inhibitor of NADPH oxidase-like flavoproteins. Cells that migrated through the stromal or endothelial layer into the wells were assayed for transendothelial migration. Results:The numbers of migrated bone marrow nuclear cells through the bEnd.3 were increased by treatment of LTB4(control, 12.5±0.2%;50nM, 22.7±0.9%;100nM, 44.3±1.4%;200nM, 36.3±0.9%;p<0.05). The numbers of migrated bone marrow nuclear cells through the MS-5 were also increased by treatment of LTB4(control, 11.0±0.9%;50nM, 25.7±0.9%;100nM, 35.8±1.8%;200nM, 32.1±0.9%;p<0.05). However, increasing effect of LTB4 to the transmi-gration of bone marrow nuclear cells through the MS-5 or bEnd.3 were inhibited by pretreatment of NAC or DPI. Conclusion:Through our data, it is suggested that LTB4 could induce the transmigration of bone marrow nuclear cells and ROS might be involved on the transendothelial migration of bone marrow nuclear cells by LTB4. It would be very interesting to test the effects of LTB4 and ROS on stem cell mobilization and homing in the future. 류코트리엔 B_(4)(LTB4)는 세포막 인지질로부터 유래된 염증과정에 관여하는 지방매개체이다1-3). LTB4의 주된 역할은 화학주성의 유도, 활성산소의 생산, 백혈구, 특히, 호중구 및 호산구의 이동에 관여하고 있으며, 내피세포와 백혈구의 부착에 중요한 역할을 하는데, 이러한 LTB4의 역할은 케모카인에 의한 백혈구의 이동과 화학주성과 많은 부분에서 유사한 특성을 가진다4-7). 염증반응과 백혈구 이동과 연관된 LTB4의 역할들은 골수내 세포들의 이동 과정에서 다른 시토카인이나 성장인자 혹은 케모카인의 역할과 유사한 점이 많다. LTB4와 비슷한 작용을 가진 여러 케모카인들이 조혈모세포를 포함한 골수내 세포들의 이동과 연관이 있음이 최근 밝혀짐에 따라, LTB4도 골수내 세포의 이동에 관련이 있을 가능성이 있다8-14). 활성산소종(ROS)은 여러 종류의 성장인자, 시토카인, 혹은 호르몬 등으로 유도된 조혈세포내 신호전달체계에 중요한 역할을 하고, 조혈세포내 여러 생명현상의 조절과 관련이 있다15-18). 특히, 염증세포에서 분비된 시토카인 혹은 케모카인들이 세포내 ROS를 증가시키고, 이때 증가된 ROS는 혈관내피세포 단층의 투과성을 증가시켜 백혈구의 경내피세포 이행을 용이하게 한다19-22). 조혈모세포 이식 후 조혈모세포가 말초혈액에서 골수 내로 자리잡는 귀소나, 골수내 조혈모세포를 혈액으로 나오게 하는 가동화의 과정은 매우 복잡하여, 여러 다양한 기전들이 관련이 있지만, 혈관내피세포 및 기질세포와 골수 조혈세포들과의 유기적인 반응과 골수 조혈세포의 경내피세포 이행이 중요한 역할을 한다23)24). 본 연구에서는 골수유핵세포의 경내피세포 및 경기질세포 이행에 LTB4와 ROS가 어떻게 영향을 미치는지 알아보고자 하였다.

침습성 아스페르길루스증으로 치료받았던 급성 백혈병 환자에서 조혈모세포이식후 발생한 파급성 아스페르길루스증 1례

배기선,박지영,신수연,문영철,최희정,조민선,성주명 대한감염학회 2003 감염과 화학요법 Vol.35 No.4

본 증례는 침습성 아스페르길루스증의 과거력을 갖고 있는 백혈병환자에서 조혈모세포이식을 받은 후 치명적인 파급성 아스페르길루스증이 발병한 예이다. 환자는 항암요법 후 흉부 방사선 및 단층촬영에서 진균성 폐렴을 의심하여 항진균제를 투여하고 폐엽절제술을 시행하여 아스페르길루스에 의한 폐렴임을 확인하였다. Amphotericin B로 치료한 후 조혈모세포이식을 시행받은 뒤 치료에도 불구하고 파급성 아스페르길루스증으로 진행되어 사망하였다. 이 증례에서 보듯이 이전에 아스페르길루스증의 과거력이 있는 경우에 이식후 치명적인 결과를 유발할 수 있으므로, 고위험군을 선별하는 지침과 적절한 치료법에 대한 연구가 필요하겠다. Invasive aspergillosis has been increasing as the number of severe immunocompromised hosts rises. Particularly, in allogeneic hematopoietic stem cell transplantation (HSCT) recipients, incidence of invasive aspergillosis ranges from 4 to 10%. Even with appropriate treatment, the prognosis of invasive aspergillosis in allogeneic HSCT recipients remains poor, showing high mortality rate. Herein. we report a case where invasive aspergillosis in a patient with acute myelogeneous leukemia progressed to disseminated aspergillosis after allogeneic HSCT. A 31-year-old woman with acute myelogenous leukemia had invasive aspergillosis after third reinduction chemotherapy. After administering amphotericin B, the patient underwent the wedge resection of lung. and HLA-matched allogeneic HSCT was then conducted. On day 14 of transplantation, the patient died of disseminated aspergillosis, including possible cerebritis and endocarditis despite the amphotericin B therapy.

Establishment of Effective B Lymphocyte Ex vivo Expansion on Human Cord Blood Using TPO, SCF, FL, IL-4, IL-10, and CD40L

Yeung Chul Mun,Kyoung Eun Lee,Jung Mi Kwon,Seung Hyun Nam,Eum Sun Yoo,Yun Kyung Bae,Seung Eun Lee,Jee Young Ahn,Soon Nam Lee,Chu Myong Seong 대한내과학회 2004 대한내과학회 추계학술대회 Vol.2004 No.1

signaling Mechanisms of Auti-proliferation by Sphingosine 1-phoshate(S1P) on Acute Promyelocytic Leukemia(APL) Cell Lines

Yeung Chul Mun,Kyoung Eun Lee,Jung Mi Kwon,Seung Hyun Nam,Eun Sun Yoo,Yun Kyung Bae,Seung Eun Lee,Jee Young Ahn,Soon Nam Lee,Chu Myoung Seong 대한내과학회 2004 대한내과학회 추계학술대회 Vol.2004 No.1

Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species

Mun, Yeung-Chul,Ahn, Jee Young,Yoo, Eun Sun,Lee, Kyoung Eun,Nam, Eun Mi,Huh, Jungwon,Woo, Hyun Ae,Rhee, Sue Goo,Seong, Chu Myong Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.9

NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2', 7'-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX™ Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO<SUB>2</SUB> (Cysteine sulfinic acid, Cys-SO<SUB>2</SUB>H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO<SUB>2</SUB> form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.

Sole Trisomy 22 Not Associated with inv(16) in Myelodysplastic Syndrome

Hahm, Chorong,Hwang, Yusun,Mun, Yeung Chul,Seong, Chu Myong,Chung, Wha Soon,Huh, Jungwon 이화여자대학교 의과학연구소 2012 EMJ (Ewha medical journal) Vol.35 No.1

Trisomy 22 is closely associated with inv(16) or t(16;16) and could be a marker of cryptic rearrangement of CBFB/MYH11 in acute myeloid leukemia (AML). Trisomy 22 not associated with CBFB/MYH11 rearrangement is a rare event. Here, we report a case diagnosed as refractory anemia with excess blasts-2 (RAEB-2) with sole trisomy 22 in the absence of CBFB/MYH11 rearrangement. The cytogenetic study of bone marrow cells disclosed trisomy 22 in 10% of metaphase cells analyzed. The other chromosomal abnormalities were not found. Fluorescence in situ hybridization (FISH) using CBFB/MYH11 probe to detect cryptic inv(16)(p13q22) showed negative result. We also excluded rearrangements of chromosome 5, 7, 8, 20, and ETV6 by FISH. Sole trisomy 22 not associated with inv(16) is a true entity.

Interleukin-1으로 유도된 흰쥐 급성폐손상에서 neutrophil elastase 억제제인 ICI 200,355의 효과

정진홍,문영철,박혜정,신경철,이관호 영남대학교 의과대학 2002 Yeungnam University Journal of Medicine Vol.19 No.1

Background: Interleukin-1(IL-1) and neutrophil appear to contribute to the pathogenesis of acute respiratory distress syndrome(ARDS). Elastase, as well as reactive oxygen species released from activated neutrophil, are thought to play pivotal roles in the experimental models of acute lung leak. This study investigated whether ICI 200,355, a synthetic elastase inhibitor, can attenuate acute lung injury induced by IL-1 in rats. Materials and Methods: We intratracheally instilled either saline of IL-1 with and without treatment of ICI 200,355 in rats. Lung lavage neutrophils, lung lavage cytokine-induced neutrophil chemoattractant(CINC) concentration, lung lavage protein concentration, lung myeloperoxidase(MPO) activity and lung leak index were measured at 5 hours of intratracheal treatment. Results: In rats given IL-1 intratracheally, lung lavage neutrophils, lung lavage CINC concentration, lung lavage protein concentration, lung MPO activity and lung leak index were higher. Intratracheal ICI 200,355 administration decreased lung lavage neutrophils, lung MPO activity and lung leak index, respectively, but did not decrease lung lavage CINC concentration. Conclusion: These results suggest that ICI 200,355 decreases lung inflammation and leak without decreasing lung lavage CINC concentration in tats given IL-1 intratracheally.

Characterization of phenotypically distinct B-cell subsets and receptor-stimulated mitogen-activated protein kinase activation in human cord blood B cells

Ha, Yun Jung,Mun, Yeung-Chul,Seong, Chu-Myong,Lee, Jong Ran Wiley (John WileySons) 2008 Journal of Leukocyte Biology Vol.84 No.6

Effect of anemia correction on Left ventricular structure and filling pressure in anemic patients without overt heart disease

( In Jeong Cho ),( Yeung Chul Mun ),( Ki Hwan Kwon ),( Gil Ja Shin ) 대한내과학회 2014 The Korean Journal of Internal Medicine Vol.29 No.4

Background/Aims: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. Methods: In total, 34 iron-deficiency anemia patients (35 ± 11 years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. Results: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/E`), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E` also decreased, suggesting a decrease in LV filling pressure. Conclusions: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E`.

Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Young Hoon Park,Dae-Young Kim,Yeung-Chul Mun,Eun Kyung Cho,Jae Hoon Lee,Deog-Yeon Jo,Inho Kim,Sung-Soo Yoon,Seon Yang Park,Byoungkook Kim,Soo-Mee Bang,Hawk Kim,Young Joo Min,Jae Hoo Park,Jong Jin Seo 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.4

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/ retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse- free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10- year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions: Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.