• Title/Summary/Keyword: Complement component 3

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A Novel Complement Fixation Pathway Initiated by SIGN-R1 Interacting with C1q in Innate Immunity

  • Kang, Young-Sun
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2008.05a
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    • pp.23-25
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    • 2008
  • Serum complement proteins comprise an important system that is responsible for several innate and adaptive immune defence mechanisms. There were three well described pathways known to lead to the generation of a C3 convertase, which catalyses the proteolysis of complement component C3, and leads to the formation of C3 opsonins (C3b, iC3b and C3d) that fix to bacteria. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial-binding C3 fragments recognized by leukocytes. The spleen clears microorganisms from the blood. Individuals lacking this organ are more susceptible to Streptococcus pneumoniae. Innate resistance to S. pneumoniae has previously been shown to involve complement components C3 and C4, however this resistance has only a partial requirement for mediators of these three pathways, such as immunoglobulin, factor B and mannose-binding lectin. Therefore it was likely that spleen and complement system provide resistance against blood-borne S. pneumoniae infection through unknown mechanism. To better understand the mechanisms involved, we studied Specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1. SIGN-R1, is a C-type lectin that is expressed at high levels by spleen marginal-zone macrophages and lymph-node macrophages. SIGN-R1 has previously been shown to be the main receptor for bacterial dextrans, as well as for the capsular pneumococcal polysaccharide (CPS) of S. pneumoniae. We examined the specific role of this receptor in the activation of complement. Using a monoclonal antibody that selectively downregulates SIGN-R1 expression in vivo, we show that in response to S. pneumoniae or CPS, SIGN-R1 mediates the immediate proteolysis of C3 and fixation of C3 opsonins to S. pneumoniae or to marginal-zone macrophages that had taken up CPS. These data indicate that SIGN-R1 is largely responsible for the rapid C3 convertase formation induced by S. pneumoniae in the spleen of mice. Also, we found that SIGN-R1 directly binds C1q and that C3 fixation by SIGN-R1 requires C1q and C4 but not factor B or immunoglobulin. Traditionally C3 convertase can be formed by the classical C1q- and immunoglobulin-dependent pathway, the alternative factor-B-dependent pathway and the soluble mannose-binding lectin pathway. Furthermore Conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-$R1^+$ spleen macrophages, and formation of C3 ligands. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. We propose that in the SIGN-R1 mediated complement activation pathway, after binding to polysaccharide, SIGN-R1 captures C1q. SIGN-R1 can then, in association with several other complement proteins including C4, lead to the formation of a C3 convertase and fixation of C3. Therefore, this new pathway for C3 fixation by SIGN-R1, which is unusual as it is a classical C1q-dependent pathway that does not require immuno globulin, contributes to innate immune resistance to certain encapsulated microorganisms.

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A Korean familial case of hereditary complement 7 deficiency (선천성 보체 7번 결핍을 가진 한국인 한 가족)

  • Kim, Moon Kyu;Lee, Kyung Yul;Lee, Jun Hwa
    • Clinical and Experimental Pediatrics
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    • v.52 no.6
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    • pp.721-724
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    • 2009
  • Meningococcal infections can be associated with abnormalities of the complement system, which contains 5 terminal complement proteins. Furthermore, deficiencies in 1 of these 5, complement component 7 (C7), leads to the loss of complement lytic function, and affected patients show increased susceptibility to recurrent meningococcal meningitis and systemic Neisseria gonorrhoeae infection. In September 2003, an 11-year-old female patient presented at our outpatient department with high fever, lower leg pain, headache, and petechiaes. She rapidly progressed to coma but later achieved full recovery due to prompt treatment. Her final diagnosis was meningococcal sepsis and arthritis. Her elder brother also had a similar bacterial meningoencephalitis history, which encouraged us to perform analyses for complement component and gene mutations. Resultantly, both the brother and sister were found to have the same mutation in the C7 gene. Subsequently, vaccinations of the meningococcal vaccine meningococcal vaccine ($Menomune^{(R)}$) were administered. However, in September 2006, the brother expired due to acute micrococcus meningoencephalitis. At present, the 16-year-old female patient is healthy. Here, we report a Korean family with a hereditary C7 deficiency with susceptibility to meningococcal infections due to C7 gene mutation.

The Expression Analysis of Complement Component C3 during Early Developmental Stages in Olive Flounder (Paralichthys olivaceus)

  • Lee, Jang-Wook;Lee, Young Mee;Lee, Jeong-Ho;Noh, Jae Koo;Kim, Hyun Chul;Park, Choul-Ji;Park, Jong-Won;Hwang, In Joon;Kim, Sung Yeon
    • Development and Reproduction
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    • v.17 no.4
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    • pp.311-319
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    • 2013
  • Fish larvae are immediately exposed to microbes from hatching to maturation of their lymphoid organs, therefore effective innate mechanisms is very important for survival in such an environment. The key component of innate immune system, C3 is central protein of all activation pathways of the complement system, leading to inflammatory reactions, such as opsonisation, chemotaxis, and cell lysis of pathogens. Although, innate mechanisms is essential for survival in the early stage of development, little is known about defence mechanisms. In this study, the alignment analysis showed that amino acid sequence of C3 from olive flounder liver EST homologous to other known C3 sequences with 73-99% identity. Also, we examined the tissue distribution of olive flounder C3 and analyzed expression pattern from the fertilized egg until 28 days post hatching. As a result, olive flounder C3 mRNA was expressed only in the liver and the mRNA level more increased as developmental proceed during the early stage. These results may suggest that olive flounder C3 plays an important function in the early immune response of olive flounder larvae.

Identification of Inflammation-related Genes Altered in the Cystic Ovary and Endometritis of Korean Cattle (난소낭종 및 자궁내막염 한우에서 염증유래 유전자 발굴)

  • Choe, Chang-Yong;Park, Sun-Young;Kim, Eun-Sook;Moon, Yoon-Ja;Park, Hye-Jin;Son, Dong-Soo;Cho, Sang-Rae;Kim, Hyun-Jong;Kim, Jae-Bum;Park, Jae-Yong;Hong, Seong-Geun;Han, Jae-Hee;Kang, Da-Won
    • Journal of Embryo Transfer
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    • v.23 no.3
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    • pp.211-216
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    • 2008
  • This study was carried out to investigate inflammation-related gene expression altered in ovary and endometrium of Korean cattle with reproductive disorders using microarray. In the present study, nine inflammation-related differential1y expressed genes (DEGs) were identified in the cystic ovary and endometrium with endometritis. In the follicular cyst, eotaxin and alpha-2-HS-glycoprotein (AHSG) were up-regulated, whereas complement component 3 (C3) and oxidised low density lipoprotein (lectin-like) receptor 1 (OLR1) were down-regulated. Complement component 4A (C4A) was up-regulated in luteal cyst. In the endometritis, chemokine 1igand l and 2 (CXCL1 and CXCL2), protein C (inactivator of coagulation factors Va and VIIIa), and complement component C5 were up-regulated, whereas kininogen was down-regulated. Of these genes, we focused on eotaxin and kininogen, which were highly regulated in the follicular cyst and endometritis, respectively and on C3 commonly regulated in both reproductive disorders. The microarray data of eotaxin, kininogen, and C3 were validated by semi-quantitative PCR. Consistent with microarray data, eotaxin was up-regulated by 4-fold in the follicular cyst, while kininogen was down-regulated by 5-fold in the endometritis. C3 was down-regulated in the both follicular cyst and endometritis. Our results suggest that these inflammation-related genes could be useful markers for diagnosis of cystic ovary and endometritis of Korean cattle.

Studies on Modified Complement Fixation Test of Bovine Blackleg (우기종저(牛氣腫疽)의 개량보체결합반응(改良補體結合反應)에 관한 연구(硏究))

  • Seo, Boo Kap
    • Korean Journal of Veterinary Research
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    • v.12 no.1
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    • pp.97-119
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    • 1972
  • Studies on modified complement fixation (MCF) test of antiblackleg bovine serum were made and the results obtained were summarized as followings. 1. The most satisfactory antigen for the MCF test among various materials studied was found to be the vegetative cells of Cl, chauvoei grown in cooked meat medium (CMM) containing 0.5mM l-(alpha) alanine and 0.1mM manganese. The antigen was prepared by inoculating the spores of Cl. chauvoei, heated at $70^{\circ}C$. for 30 minutes, into the CMM followed by incubation at $37^{\circ}C$. for 15 hours. 2. An active component contained in the factor serum of fresh normal rabbit serum was found to be C'4 fraction. It was also shown that, furthermore, DEAE cellulose sieved C'4 fraction of the factor serum enhanced antibody titer and the highest antibody titer was resulted by the addition of 0.03 ml, of the factor serum to each tube. 3. More than four fold increases of antibody titer, in antiblbckleg bovine serum-antigen system, was made with the MCF test than that with the direct complement fixation test. 4. The MCF antibody titer of cattle vaccinated against blackleg was 128 until seven month and 64 for five months thereafter.

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FREE AND NEARLY FREE CURVES FROM CONIC PENCILS

  • Dimca, Alexandru
    • Journal of the Korean Mathematical Society
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    • v.55 no.3
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    • pp.705-717
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    • 2018
  • We construct some infinite series of free and nearly free curves using pencils of conics with a base locus of cardinality at most two. These curves have an interesting topology, e.g. a high degree Alexander polynomial that can be explicitly determined, a Milnor fiber homotopy equivalent to a bouquet of circles, or an irreducible translated component in the characteristic variety of their complement. Monodromy eigenspaces in the first cohomology group of the corresponding Milnor fibers are also described in terms of explicit differential forms.

Invariant Trace Fields of Chain Links

  • Ryou, Kazuhiro
    • Kyungpook Mathematical Journal
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    • v.56 no.1
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    • pp.257-271
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    • 2016
  • In this paper, we compute the trace field of C(2, s), the complement of two component chain link with s left half twists in ${\mathbb{S}}^3$, for every s. As a result, for every $n{\in}{\mathbb{N}}{\backslash}\{1\}$, we can find $s{\in}{\mathbb{Z}}$ such that the degree of the trace field of C(2, s) is n. We also prove that if for fixed p, the degree of the trace field of C(p, s) runs over ${\mathbb{N}}{\backslash}\{1\}$, then p is contained in {1, 2, 4, 8}.

Identification of Business Component based on Independence Metric (독립척도 기반의 비즈니스 컴포넌트 식별)

  • Choi, Mi-Sook;Cho, Eun-Sook
    • The KIPS Transactions:PartD
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    • v.11D no.3
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    • pp.625-634
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    • 2004
  • When constructing a component based system, It is understood that identifying reusable and independent business components is of utmost importance. However, according to conventional component based developing methodologies, most of developers depend on their experience and/or intuition for identification of business components. Furthermore, there are no criteria to evaluate whether the identified business components are more independently defined or not. Therefore, we propose a component identification metrics to apply to component properties In order to complement the difficulties of identifying business components through developers' experience and/or intuition. The metrics defined are the criteria for identifying the business Components and/or for evaluating the Identified components. We propose both a cohesion metric, and a coupling metric, to which component properties are applied, wherein those properties can be understood by high cohesion in, and low coupling between, components. Moreover, we propose an independence metric that can evaluate the degree of independence for a particular component by ratio of the cohesion and coupling of components. The metrics that we propose are applied to case study which demonstrates the identification of more independent business components and the validity of our metrics.

Cloning of the Genomic DNA Which Complements the Drug-Hypersensitivity of Saccharomyces cerevlsiae

  • Lee, Yun-Sik;Park, Kie-In
    • BMB Reports
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    • v.30 no.3
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    • pp.167-172
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    • 1997
  • The yeast Saccharomyces cerevisiae, mutant CH117, shows a drug-hypersensitivity (dhs) to cycloheximide, bleomycin, actinomycin D, 5-fluorouracil. nystatin, nigericin and several other antibiotics. CH 117 was also temperature-sensitive (ts). being unable to grow at $37^{\circ}C$ and secreted more invertase and acid phosphatase into the medium than the parent yeast. CH117 grows very slowly and the cell shape is somewhat larger and more sensitive to zymolyase than the wild type cells. Light microscopic and electron microscopic observation also revealed abnormality of the mutant cell wall. These characteristics indicate that CH117 has a defect in an essential component of the cell surface and that the cell wall which performs barrier functions has become leaky in the mutant. We screened a genomic library of wild type yeast for clones that can complement the mutation of CH117. A plasmid, pCHX1, with an insert of 3.6 kilobases (kbs) could complement the dhs and ts of CH117. Deletion and subcloning of the 3.6 kb insert showed that a gene for the complementation of mutant phenotypes was located in 1.9 kbs Puvll-Hindlll fragment.

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Effects of Artificial Digestive Juice on the Antitumor-Immunity Activity of Protein-bound Polysaccharide from Ganoderma lucidum (인공소화액이 영지 단백 다당체의 항암-면역 활성에 미치는 영향)

  • 유정실;현진원;김하원;심미자;김병각
    • YAKHAK HOEJI
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    • v.44 no.4
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    • pp.347-353
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    • 2000
  • To examine influence of artificial digestive juice on the antitumor activity of Ganoderma lucidum-A(GL-A), protein-bound polysaccharide from Ganoderma lucidum, we compared the digested protein-bound polysaccharide with undigested one both on immunopotentiating activity and influence of digestive juices. Protein-bound polysaccharide GL-B was obtained by digesting the antitumor component GL-A with artificial digestive Juices in vitro. When GL-A was administered orally to sarcoma 180 tumor-bearing ICR mice, the life prolonging effect was exhibited in a dose dependent manner Not only GL-A but GL-B increased the production of colony forming unit (CFU) to 10- and 8-fold of that of the control, respectively. Both of the protein-bound polysaccharides also showed the secretion of nitric oxide in RAW 264.7 cell lines to 3.5-and 3.7-fold of that of the control, respectively: GL-A activated components of the alternative complement pathway, whereas GL-B did not. In humoral immunity GL-A increased the activity of alkaline phosphatase in differentiated B cells to 3 times and GL-B to 4 times of that of the control. These results showed that the artificial digestive juices had no influence on the antitumor activity of the protein-bound polysaccharide from Ganoderma lucidum and that its immunomodulating activity retained after treatment with artificial digestive juice. And this provides a basis of the protein-bound polysaccharide of Ganoderma lucidum as an peroral anticancer drug.

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