• 제목/요약/키워드: Complement component 3

검색결과 36건 처리시간 0.023초

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

  • Kang, Young-Sun
    • 한국미생물학회:학술대회논문집
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    • 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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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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선천성 보체 7번 결핍을 가진 한국인 한 가족 (A Korean familial case of hereditary complement 7 deficiency)

  • 김문규;이경열;이준화
    • Clinical and Experimental Pediatrics
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    • 제52권6호
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    • pp.721-724
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    • 2009
  • 수막구균(Meningococcus) 질환은 보체계의 이상과 관련이 있을 수 있다. 보체 7번은 5개의 말단 보체 단백질(terminal complement protein) 중 하나로 이것이 결핍되면 보체의 세포를 용해하는 작용을 잃게 되어 반복적인 감염, 특히 수막구균 감염에 대한 감수성이 증가한다. 2003년 9월 고열, 하지 동통, 두통과 점상 출혈로 외래에 내원한 11세 된 여자 환자가 입원 후 급격히 혼수 상태로 빠졌으나 즉각적인 치료로 결국 완전히 회복되었다. 환자의 최종 진단은 수막구균성 패혈증과 관절염이었다. 환자의 오빠도 비슷한 세균성 뇌수막염 가족력이 있어 저자들은 보체계 검사와 유전자 돌연변이(gene mutation)에 대해 분석하였고, 환자와 환자의 오빠는 보체 7번 유전자의 exon 4에 G394C에 돌연변이가 있는 선천성 보체 7번 결핍 환자였고, 아빠는 보인자로 밝혀졌다. 저자들은 예방적으로 4가 수막구균 백신(tetravalent polysaccharide meningococcal vaccine, $Menomune^{(R)}$ A/C/Y/W-135, Aventis Pasteur, Canada)을 3년마다 접종하기로 하였고 2004년 10월에 처음으로 접종하였다. 그러나 2006년 9월 오빠는 급성 세균성 뇌수막염(meningoencephalitis)으로 사망하였다. 이에 저자들은 2년마다 예방적 접종을 하기로 하였고, 환자는 2008년 9월에 3번째로 접종하였으며 16세 된 환자는 현재까지 건강한 상태이다. 저자들은 수막구균 감염과 보체 7번 유전자 네번째 intron의 3' 말단 splice acceptor 위치에 G to T 돌연변이(g.IVS4-1G> T)가 있는 선천성 보체 7번 결핍을 가진 한국인 한 가족을 보고하는 바이다.

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
    • 한국발생생물학회지:발생과생식
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    • 제17권4호
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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.

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

  • 최창용;박선영;김은숙;문윤자;박혜진;손동수;조상래;김현종;김재범;박재용;홍성근;한재희;강다원
    • 한국수정란이식학회지
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    • 제23권3호
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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.

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

  • 서부갑
    • 대한수의학회지
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    • 제12권1호
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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
    • 대한수학회지
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    • 제55권3호
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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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    • 제56권1호
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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}.

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

  • 최미숙;조은숙
    • 정보처리학회논문지D
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    • 제11D권3호
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    • pp.625-634
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    • 2004
  • 컴포넌트 아키텍쳐 설계를 위하여 재사용 가능한 독립적인 비즈니스 컴포넌트의 식별은 컴포넌트 기반 시스템 구축을 위하여 가장 중요한 작업이다. 그러나 기존 컴포넌트 기반 개발 방법론들의 컴포넌트 시별 방법은 대다수 개발자의 직관과 경험에 의존하고 있다. 또한 개발자들에 의해서 식별된 컴포넌트가 보다 독립적으로 잘 정의되었는지 평가할 기준이 없다. 따라서 본 논문에서는 개발자의 직관과 경험에 의존하는 비즈니스 컴포넌트 식별의 어려운 점을 보완하기 위하여 비즈니스 컴포넌트 식별의 평가 기준이 되는 메트릭을 컴포넌트의 특성을 부여하여 정의한다. 즉, 비즈니스 컴포넌트 식별을 위하여 컴포넌트 내의 응집도는 높고 컴포넌트 간의 결합도는 낮아야 하는 컴포넌트 특성을 적용한 응집척도와 결합척도를 제안한다. 또한 컴포넌트의 응집도와 결함도의 비율에 의하여 비즈니스 컴포넌트의 독립의 정도를 평가할 수 있는 독립척도를 제안한다. 본 논문에서 제안한 응집척도, 결합척도 그리고 독립척도를 사례에 적용하여 그 효율성을 평가한다.

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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    • 제30권3호
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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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인공소화액이 영지 단백 다당체의 항암-면역 활성에 미치는 영향 (Effects of Artificial Digestive Juice on the Antitumor-Immunity Activity of Protein-bound Polysaccharide from Ganoderma lucidum)

  • 유정실;현진원;김하원;심미자;김병각
    • 약학회지
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    • 제44권4호
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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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