• Title, Summary, Keyword: complement

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The Role of Complement in the Immunologic Microenvironment of Tumor Cells: Potential Therapeutic Targets

  • Jo, Kyeong Beom;Snape, Alison
    • Microbiology and Biotechnology Letters
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    • v.44 no.4
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    • pp.420-431
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    • 2016
  • The complement system comprises a set of essential molecules that bridge the innate and adaptive immune responses. Research has focused on how the complement system's destructive mechanism could potentially be harnessed for cancer treatment. However, cancer subverts the complement system to avoid immunosurveillance. In addition, a complement-triggered biological mechanism that contributes to cancer growth has been identified. Thus, drugs should be designed to homeostatically maintain a normal concentration of complement. This review explores three types of complement-related anti-cancer drugs: therapeutic antibodies, complement inhibitory drugs, and anti-complement regulatory drugs.

Complement regulation: physiology and disease relevance

  • Cho, Heeyeon
    • Clinical and Experimental Pediatrics
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    • v.58 no.7
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    • pp.239-244
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    • 2015
  • The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.

Susceptibility of KSHV-Infected PEL Cell Lines to the Human Complement System

  • Yoo, Seung-Min;Jeon, Hyungtaek;Lee, Suhyuk;Lee, Myung-Shin
    • Journal of Microbiology and Biotechnology
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    • v.26 no.3
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    • pp.618-626
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    • 2016
  • Pleural effusion lymphoma (PEL) is a rare B-cell lymphoma that has a very poor prognosis with a median survival time of around 6 months. PEL is caused by Kaposi's sarcoma-associated herpesvirus, and is often co-infected with the Epstein Barr virus. The complement system is fundamental in the innate immune system against pathogen invasion and tumor development. In the present study, we investigated the activation of the complement system in PEL cells using human serum complements. Interestingly, two widely used PEL cell lines, BCP-1 and BCBL-1, showed different susceptibility to the complement system, which may be due to CD46 expression on their cell membranes. Complement activation did not induce apoptosis but supported cell survival considerably. Our results demonstrated the susceptibility of PEL to the complement system and its underlying mechanisms, which would provide insight into understanding the pathogenesis of PEL.

Genetic Association of the Porcine C9 Complement Component with Hemolytic Complement Activity

  • Khoa, D.V.A.;Wimmers, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.9
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    • pp.1354-1361
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    • 2015
  • The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative) leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs) in pigs of the breeds Hampshire (HS), Duroc (DU), Berlin miniature pig (BMP), German Landrace (LR), Pietrain (PIE), and Muong Khuong (Vietnamese potbelly pig). Genotyping was performed in 417 $F_2$ animals of a resource population (DUMI: $DU{\times}BMP$) that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE) show higher allele frequency of these SNPs than Vietnamese porcine breed (MK). Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9) as a candidate gene to improve general animal health in the future.

Anti-complement Activity of Phenolic Compounds from the Stem Bark of Magnolia obovata

  • Min, Byung-Sun
    • Natural Product Sciences
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    • v.14 no.3
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    • pp.196-201
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    • 2008
  • Five neolignans (1 - 4, 8), two sesquiterpene-lignans (5 - 6), and two phenylpropanoids (7, 9) were isolated from the stem bark of Magnolia obovata Thunberg (Magnoliaceae) by repeated column chromatography. The structures of isolated compounds were identified as 4-methoxyhonokiol (1), obovatol (2), magnolol (3), honokiol (4), eudeshonokiol B (5), eudesobovatol B (6), coumaric acid (7), magnaldehyde B (8), and ${\rho}-coumaric$ acid (9) on the basis of spectroscopic analysis including 2D-NMR and MS data. Compounds 1 - 9 were evaluated for their anti-complement activities against the classical pathway of the complement system. Of them, compound 8 showed significant anti-complement activity on the classical pathway with $IC_{50}$ value of 102.7 ${\mu}M$, whereas compounds 1 - 7 and 9 were inactive. This result indicated that an aldehyde group in the neolignan is important for the anti-complement activity against the classical pathway.

Atypical Hemolytic Uremic Syndrome in a 13-year-old Lao Girl: A Case Report

  • Kedsatha, Philavanh;Cheong, Hae Il;Choi, Yong
    • Childhood Kidney Diseases
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    • v.23 no.1
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    • pp.43-47
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    • 2019
  • Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy, is distinguished from the typical form by the absence of a preceding verotoxin-producing Escherichia coli infection. Notably, aHUS occurs in association with genetic or acquired disorders causing dysregulation of the alternative complement pathway. Patients with aHUS may show the presence of anti-complement factor H (CFH) autoantibodies. This acquired form of aHUS (antiCFH-aHUS) primarily affects children aged 9-13 years. We report a case of a 13-year-old Lao girl with clinical features of aHUS (most likely anti-CFH-aHUS). The initial presentation of the patient met the classical clinical triad of thrombotic microangiopathy (microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury) without preceding diarrheal illness. Low serum levels of complement 3 and normal levels of complement 4 indicated abnormal activation of the alternative complement pathway. Plasma infusion and high-dose corticosteroid therapy resulted in improvement of the renal function and hematological profile, although the patient subsequently died of infectious complications. This is the first case report that describes aHUS (possibly anti-CFH-aHUS) in Laos.

Linguistic Description and Theory

  • Nakajima, Heizo
    • Korean Journal of English Language and Linguistics
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    • v.1 no.3
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    • pp.349-368
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    • 2001
  • We have brought up several distinct types of English clausal constructions, and have been lead to the descriptive generalization in (14),repeated here as (33): (33) Reduced clauses cannot occur in non-complement positions. The generalization in (33) refers to two theory-internal notions, reduced clauses and non-complement positions. Both notions are concerned with the composition of syntactic structures to be defined by X-bar theory. Without these theoretical notions, it would be difficult to describe in a general form the fact that certain types of complement clauses-namely, null-that clauses, if-clauses, Acc-ing gerund, ECM complement clauses, and Raising complement clauses-cannot occur in particular syntactic positions. Instead, one would have to describe this fact for each clause type, in such a way that null-that clauses cannot occur in such and such positions, and if-clauses cannot occur in such and such positions, and Acc-ing gerund cannot occur in such and such positions, and so on, although the positions in which they cannot occur are totally the same. Given the terminology of X-bar theory, however, it has turned out that these types of complement clauses are all reduced clauses, and the positions where they cannot occur are all non-complement positions. Then, the generalization has obtained that reduced clauses cannot occur in non-complement positions. It is a theoretical issue, and differs depending upon theories, how to explain why such a descriptive generalization holds at all. Hopefully, the demonstration here provides a piece of evidence showing that a theory or a particular theoretical nation plays an important role in the description of linguistic facts. Moreover, I have made a crucial prediction on the basis of the well-accepted theoretical assumption the ECM complement clauses and Raising complement clauses are reduced clauses; namely, the prediction that these types of clauses cannot occur in non-complement position. The prediction based upon the theoretical assumption is actually borne out, as illustrated earlier. The illustration of the prediction, I hope, shows that a theory or a particular theoretical assumption, coupled with another theoretical assumption, allows us to make some interesting predictions. Predictions serve to widen a range of linguistic facts to be described. A theory plays a crucial part in finding out interesting facts as well as in describing them in some general forms. Finally, let me state a few words as to the recent generative theory in connection with linguistic description. The recent generative theory is getting more and more abstract. I think it is moving toward a good direction as cognitive science. It will contribute, among others, to the inquiry into what is knowledge that is very specific to language faculty, and into how it interacts with other cognitive faculties. However, I am suspicious about how much the abstract generative theory will contribute to the description of linguistic facts in a particular language. While generative theory is claimed to aim both for descriptive adequacy and for explanatory adequacy, the recent generative theory is likely to put much more weight on explanatory adequacy. In my view, a less abstract theory is enough, or even more useful, for the purpose of linguistic description. Of course, how abstract theory one should adopt as a framework differs depending upon what aspect of language one attempts to describe. What I would like to emphasize here is that linguistic theory does not conflicts with linguistic description, and a linguistic theory with an appropriate degree of abstractness serves as a tool for finding out new interesting facts, as well as for describing them in some general, elegant forms.

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A Study on Effect to Complement Activation and Pulmonary Leukostasis During Cardiopulmonary bypass: Comparison of Bubble Oxygenator and Membrane Oxygenator (체외순환이 보체활성화화 백혈구의 폐내 정체에 미치는 영향에 관한 연구)

  • Kim, Yang-Won;Choe, Seok-Cheol;Jo, Gwang-Hyeon
    • The Korean Journal of Thoracic and Cardiovascular Surgery
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    • v.28 no.7
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    • pp.649-657
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    • 1995
  • From December 1993 to April 1994, to investigate complement activation and pulmonary leukostasis, thirty adult patients were studied during cardiopulmonary bypass[CPB for cardiac surgery in Department of Cardiovascular & Thoracic Surgery, Pusan Paik Hospital, Inje University. Total patients were divided into group I and II according to the purpose of study ; Group I was 15 patients undergoing CPB with bubble oxygenator, Group II was 15 patients undergoing CPB with membrane oxygenator. The results of study were summarized as follows.1. The decrease of C3 and C4 levels were observed within few minutes of beginning of CPB in all patients[P<0.05 , and this decrease was proved to be due to complement activation, not by the influence of hemodilution.2. In the correlation between the change of C3 and C4, group I showed linear correlation each other suggesting complement activation occurred through the classical pathway, group II showed a correlation at only partial sampling times suggesting complement activation via both classical and alternative pathway, however there was no significant statistical difference at the change of C3 and C4 concentrations in two groups[P>0.05 .3. After switching to partial CPB, a few difference between right atrial and left atrial WBC count was observed, but statistically not significant and median cell count difference between group I and II was not significant, too [P>0.05 . With the above result, we concluded that CPB itself contributes to the activation of complement system, but bubble oxygenator does not activate always complement system more than membrane oxygenator.

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A Study on the design of two's complement bit-serial FIR filter with systolic array architecture (Systolic Array를 이용한 Two's Complement Bit-Serial Fir 필터 설계에 관한 연구)

  • 엄두섭;박노경;차균현
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.14 no.5
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    • pp.442-452
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    • 1989
  • This Paper describes the impleentation of two's complement bit-serial FIR filter with systolic architectur. The filter coefficients are represented as sign and magnitude form and the input data is represented as two's complement form. We use systolic array to obtain high operation speed so this FIR filter sucessfully operates in real-time environment.

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