SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen

MG Prabagar,Y Do,S Ryu,J-Y Park,H-J Choi,W-S Choi,TJ Yun,J Moon,I-S Choi,K Ko,K Ko,C Young Shin,C Cheong,Y-S Kang 한국당과학회 2013 한국당과학회 학술대회 Vol.2013 No.1

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-β in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen

Prabagar, M G,Do, Y,Ryu, S,Park, J-Y,Choi, H-J,Choi, W-S,Yun, T J,Moon, J,Choi, I-S,Ko, K,Ko, K,Young Shin, C,Cheong, C,Kang, Y-S Macmillan Publishers Limited 2013 Cell death and differentiation Vol.20 No.4

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1–C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-β in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

소디움알파술폰 고급지방산 모노글리세리드의 세정성

노윤찬,이승렬,윤영균,남기대 ( Y . C . Ro,S . Y . Lee,Y . K . Yun,K . D . Nam ) 한국공업화학회 1994 공업화학 Vol.5 No.5

새로운 기능성을 갖는 sodium monogtycerol α-sulfonated alkanonate류에서 소수성 부분의 알킬기의 탄소수에 따른 세정력을 비교한 결과 C_(16)>C_(18)>C_(14)>C_(12)의 순으로 나타났고, 이들 중 세정력이 가장 우수한 sodium monoglycerol α-sulfonated hexadecanonate는 무공해 세정제로서 기대성이 있는바 현재 공업적으로 대량 사용하고 있는 sodium α-sulfonated alkanoic acid methyl ester와 sodium alkyl benzene sulfonate를 상대 비교한 결과, 보다 우수한 세정력을 나타내며 공업적 응용성에 기대성이 크다. The detergencies of these new functional anionic surfactants, sodium monoglycerol α-sulfonated alkanoates, were investigated and compared with those of two commercial surfactants, that is, sodium α-sulfonated alkanoic acid methyl ester and sodium alkyl benzene sulfonate. According to the variation of the hydrophobic alkyl chain length, the order of detergency was shown to be C_(16)>C_(18)>C_(14)>C_(12). From the comparision experiment for the detergency and the various fundamental properties of two other surfactants, it was found that sodium monoglycerol α-sulfonated hexadecanonate has the most outstanding characteristics of detergency. Possibly this result shows light on its industrial application as a nonpolluting detergent.

Role of Leu188 in the Fatty Acid Hydroxylase Activity of CYP102A1 from Bacillus megaterium

Jang, H.H.,Shin, S.M.,Ma, S.H.,Lee, G.Y.,Joung, Y.H.,Yun, C.H. Elsevier 2016 Journal of molecular catalysis Enzymatic Vol.133 No.-

<P>P450 BM3 (CYP102A1) from Bacillus megaterium catalyzes the subterminal hydroxylation of fatty acids with 12-22 carbons at the omega-1, omega-2 and omega-3 positions. Several amino acids located at the substrate channel and active sites are known to be important for the catalytic activity of CYP102A1. The L188 residue at the C-terminus of alpha-helix F undergoes a large shift upon substrate binding and has frequently been found in different combinations of multiple mutations showing enhanced and altered activities. In this study, we examined the role of the L188 residue by comparing the catalytic activities of wild-type CYP102A1 and 19 mutants of L188. The mutants were made with site-directed mutagenesis and functionally expressed in Escherichia coll. The enzymatic properties of the mutants for a set of fatty acids (C-10-C-16) were compared to the properties of the wild-type. L188Q and L188 P mutants showed especially strong increases in hydroxylase activity toward C-10-C-13 fatty acids, although they did not have activity changes for C-14-C-16 fatty acids. Although most mutants showed very similar overall hydroxylation rates for myristic acid, 14 mutants showed apparent changes in the regioselectivity of hydroxylation with a preference for the omega-3 position over the omega-1 position. A possible role for the L188 residue has been discussed in the context of the structure and function of CYP102A1. (C) 2016 Elsevier B.V. All rights reserved.</P>

Production of (S)-3-hydroxybutyrate by metabolically engineered Saccharomyces cerevisiae

Yun, E.J.,Kwak, S.,Kim, S.R.,Park, Y.C.,Jin, Y.S.,Kim, K.H. Elsevier Science Publishers 2015 Journal of biotechnology Vol.209 No.-

(S)-3-Hydroxybutyrate (S-3HB) can be used as a precursor for the synthesis of biodegradable polymers such as polyhydroxyalkanoate and stereo-specific fine chemicals such as antibiotics, pheromones, and drugs. For the production of S-3HB in yeast, the biosynthetic pathway of S-3HB from acetyl-CoA, consisting of the three enzymes, acetyl-CoA C-acetyltransferase (ACCT), acetoacetyl-CoA reductase (ACR), and 3-hydroxybutyryl-CoA thioesterase (HBT), was introduced into Saccharomyces cerevisiae. An engineered yeast strain overexpressing ERG10, hbd, and tesB genes not only exhibited enzyme activities of AACT, ACR, and HBT, but also produced S-3HB from ethanol. In order to increase the titer of S-3HB, a fed-batch fermentation based on pulse feeding of ethanol as a carbon source was performed, and a final S-3HB titer of 12.0g/L was achieved. This is the first report on the production of 3HB by engineered yeast, utilizing ethanol as the carbon source, suggesting that the industrially preferred S. cerevisiae can be a promising host for producing S-3HB.

Cyclosporine 과 Methylprednisolone의 Y-site 병용 투여시의 Compatibility

윤혜영,이윤향,김운학,임성실,김옥녀 한국병원약사회 1999 병원약사회지 Vol.16 No.1

The compatibility of cyclosporine and methylprednisolone at simulated Y-site administration was studied by this research. Each cyclosporine (CP) to methylprednisolone (MP) was diluted in the concentration 0.5 ㎎/㎖ and 1.25 ㎎/㎖ respectively. As diluent, 5% dextrose water (D5W) or normal saline (NS) was used. Each the above diluted solution was mixed in the 1:1 ratio by the following compositions : a) CP/D5W + MP/D5W ; b) CP/D5W + MP/NS ; c) CP/NS + MP/D5W ; 4) CP/NS + MP/NS. After that, each mixture solution a), b), c), and d) was checked for precipitation, pH and the concentrations at 0, 0.5, 1.0, 2.0, 3.0, 4.0 hrs after mixing by the HPLC method. As the result, all of the above mixture solutions had no precipitation, and no significant pH differences (7.04∼7.30). Also, over the 4 hour study periods, the content of each cyclosporine or methylprednisolone was more than 90% at all the time. This study has been showed the diluted cyclosporine and methylprednisolone was compatible at Y-site administration, and it can be possible to apply for the further patient care.

시뮬레이션을 이용한 전동차사무소 수행도 평가

이춘우,김원영,권용주,김소영,윤초희,오세진,전태보 江原大學校 産業技術硏究所 2004 産業技術硏究 Vol.24 No.A

A performance analysis for newly being considered electric rail car office has been made in this study. The major purpose is to examine a proposed design in terms of its capacity and the proposed number of travels (82-84) per day. For this study we first examined the overall system configuration with detailed operational processes of cleaning and inspection. We then developed a simulation model using ARENA and designed input data from 12 selected factors and their interaction effects. A simulation run for each treatment combination of L_(16)(2^(15)) orthogonal array was run and 20 batch means were obtained. Through careful analyses of the results obtained, we drew a diversity of suggestions including the best factor level combination. Our confirmation experiments at the optimal level combination further validate the possibility of 82 runs and the consistency in the results.

Validation of SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) Score for Prediction of Outcomes After Unprotected Left Main Coronary Revascularization

Kim, Y.H.,Park, D.W.,Kim, W.J.,Lee, J.Y.,Yun, S.C.,Kang, S.J.,Lee, S.W.,Lee, C.W.,Park, S.W.,Park, S.J. Elsevier 2010 JACC. Cardiovascular interventions Vol.3 No.6

Objectives: This study aimed to validate the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score representing angiographic complexity after unprotected left main coronary artery (ULMCA) revascularization. Background: The validity of the SYNTAX score has been adequately evaluated. Methods: The SYNTAX scores were calculated for 1,580 patients in a large multicenter registry who underwent percutaneous coronary intervention (PCI) (n = 819) or coronary artery bypass graft (CABG) (n = 761) for ULMCA stenosis. The outcomes of interests were 3-year incidences of major adverse vascular events (MAVE), including death, Q-wave myocardial infarction, and stroke and major adverse cardiac and cerebrovascular events (MACCE), including MAVE and target vessel revascularization of ULMCA. Results: The incidence of 3-year MAVE was 6.2% in the lowest (@?23), 7.1% in the intermediate (23 to ~36), and 17.4% in the highest (>36) SYNTAX score tertile groups after PCI (p = 0.010). However, the incidences of MAVE in the CABG group and MACCE in the PCI and CABG groups did not differ among the SYNTAX tertiles. In subgroups, the MAVE (p = 0.005) and MACCE (p = 0.007) rates according to the SYNTAX score tertiles were significantly different in patients receiving drug-eluting stent, not in those receiving bare-metal stent. When compared with the clinical EuroSCORE (European System for Cardiac Operative Risk Evaluation), the C-indexes of SYNTAX score and EuroSCORE were 0.59 and 0.67, respectively, for discrimination of MAVE and 0.53 and 0.57, respectively, for MACCE. Conclusions: The angiographic SYNTAX score seems to play a partial role in predicting long-term adverse events after PCI for ULMCA stenosis. A complementary consideration of patient's clinical risk might improve the predictive ability of risk score.

Lipopolysaccharide-binding and neutralizing activities of surfactin C in experimental models of septic shock

Hwang, Y.H.,Park, B.K.,Lim, J.H.,Kim, M.S.,Park, S.C.,Hwang, M.H.,Yun, H.I. North-Holland ; Elsevier Science Ltd 2007 european journal of pharmacology Vol.556 No.1

To evaluate the anti-endotoxin activity of surfactin C, we studied its lipopolysaccharide-binding activity in vitro and therapeutic efficacy in experimental models of gram-negative septic shock. The ability of surfactin C to bind LPS from Escherichia coli O111:B4 was determined using a limulus chromogenic assay. Male ICR mice and Sprague-Dawley rats were given intraperitoneal administration of 1x10<SUP>9</SUP> colony forming units of E. coli ATCC 25922. After bacterial challenge, all animals were randomized to receive intraperitoneally saline, polymyxin B or surfactin C. Surfactin C not only completely bound to the LPS (its median effective concentration being 13.75 μM) but also improved the survival and reduced of the number of inoculated bacteria in the mouse model of septic shock. Surfactin C reduced the plasma endotoxin, tumor necrosis factor-α and nitric oxide levels in response to septic shock in rats.

Gut-Specific Delivery of T-Helper 17 Cells Reduces Obesity and Insulin Resistance in Mice

Hong, C.P.,Park, A.,Yang, B.G.,Yun, C.H.,Kwak, M.J.,Lee, G.W.,Kim, J.H.,Jang, M.S.,Lee, E.J.,Jeun, E.J.,You, G.,Kim, K.S.,Choi, Y.,Park, J.H.,Hwang, D.,Im, S.H.,Kim, J.F.,Kim, Y.K.,Seoh, J.Y.,Surh, C. Elsevier North Holland [etc.] 2017 Gastroenterology Vol.152 No.8

<P>BACKGROUND & AIMS: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4(+) T-helper (T-H) cells with obesity and the effects of gut-tropic T(H)17 cells in mice on a high-fat diet (HFD). METHODS: We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry. Mice fed a vitamin A-deficient HFD were compared with mice fed a vitamin A-sufficient HFD. Obese RAG1-deficient mice were given injections of only regulatory T cells or a combination of regulatory T cells and T(H)17 cells (wild type or deficient in integrin beta 7 subunit or interleukin 17 [IL17]). Mice were examined for weight gain, fat mass, fatty liver, glucose tolerance, and insulin resistance. Fecal samples were collected before and after T cell transfer and analyzed for microbiota composition by metagenomic DNA sequencing and quantitative polymerase chain reaction. RESULTS: Mice placed on a HFD became obese, which affected the distribution of small intestinal CD4(+) T-H cells. Intestinal tissues from obese mice had significant reductions in the proportion of T(H)17 cells but increased proportion of T(H)1 cells, compared with intestinal tissues from nonobese mice. Depletion of vitamin A in obese mice further reduced the proportion of T(H)17 cells in small intestine; this reduction correlated with more weight gain and worsening of glucose intolerance and insulin resistance. Adoptive transfer of in vitro-differentiated gut-tropic T(H)17 cells to obese mice reduced these metabolic defects, which required the integrin beta 7 subunit and IL17. Delivery of T(H)17 cells to intestines of mice led to expansion of commensal microbes associated with leanness. CONCLUSIONS: In mice, intestinal T(H)17 cells contribute to development of a microbiota that maintains metabolic homeostasis, via IL17. Gut-homing T(H)17 cells might be used to reduce metabolic disorders in obese individuals.</P>