Cleavage of Complement C3b to iC3b on the Surface of<i>Staphylococcus aureus</i>Is Mediated by Serum Complement Factor I

Cunnion, Kenji M.; Hair, Pamela S.; Buescher, E. Stephen

doi:10.1128/iai.72.5.2858-2863.2004

Cited by 50 publications

(49 citation statements)

References 23 publications

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“…Both C3 and factor B presented additional fragments, thus indicating the presence of their activation products. The patterns observed in our vitreous samples were consistent with the native α and β chains of C3 (115 and 75 kDa) and the presence of other smaller bands, with the 42 kDa fragment (corresponding to the breakdown of C3b [17]) being the most apparent. Factor B patterns showed a major band of 93 kDa and two fragments consistent with breakdown fragments of 63 kDa (Bb) and 30 kDa (Ba) [18].…”

Section: Digesupporting

confidence: 82%

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

Garcia-Ramírez

Canals

Hernández³

et al. 2007

Diabetologia

151

135

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Aims/hypothesis The aim of this study was to compare the protein profile of vitreous fluid from diabetic patients with proliferative diabetic retinopathy (PDR) with that from nondiabetic patients with idiopathic macular holes (MH). The mRNA of proteins differentially produced was also assessed in the retinas from diabetic and non-diabetic donors. Materials and methods Vitreous humour from type 1 diabetic patients with PDR (n=8) and from non-diabetic patients with MH (n=10) closely matched in terms of age were studied. The comparative proteomic analysis was performed using fluorescence-based difference gel electrophoresis (DIGE). Differentially produced proteins (abundance ratio >1.4, p<0.05) were identified by mass spectrometry. Expressions of mRNA were measured by real-time RT-PCR in retinas from ten human eyes obtained at post-mortem (five eyes from diabetic subjects and five eyes from non-diabetic subjects). Results Eight proteins were highly produced in PDR patients in comparison with non-diabetic subjects: zinc-α 2 -glycoprotein (ZAG), apolipoprotein (apo) A1, apoH, fibrinogen A, and the complement factors C3, C4b, C9 and factor B). We found three proteins that were underproduced in PDR subjects: pigment epithelial derived factor (PEDF), interstitial retinol-binding protein (IRBP) and inter-α-trypsin inhibitor heavy chain (ITIH2). There was no overlap in the vitreous levels of the above-mentioned proteins between PDR patients and non-diabetic control subjects. The differential production of ZAG, C3, factor B, PEDF and IRBP was further confirmed by western blot, and was in agreement with mRNA levels detected in the retina. Conclusions/interpretation Proteomic analysis by DIGE, which permits an accurate quantitative comparison, was useful in identifying new potential candidates involved in the pathogenesis of PDR.

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Section: Digesupporting

confidence: 82%

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

Garcia-Ramírez

Canals

Hernández³

et al. 2007

Diabetologia

151

135

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“…Normal human serum (NHS) for red blood cell (RBC) lysis experiments was isolated from the blood of healthy human volunteers in accordance with an Institutional Review Board-approved protocol (IRB 02-06-EX-0216; Eastern Virginia Medical School) and was pooled, aliquoted, and frozen at Ϫ80°C as a stock for all experiments, as previously described (6). Sheep RBCs (MP Biomedicals) were sensitized with 0.72 mg/ml anti-sheep RBC antibody (Rockland) and standardized to 5 ϫ 10 8 cells/ml with GVBS ϩϩ (Veronal-buffered saline, 0.1% gelatin, 0.15 mM CaCl 2 , and 1.0 mM MgCl 2 ).…”

Section: Methodsmentioning

confidence: 99%

Human Astrovirus Coat Protein Inhibits Serum Complement Activation via C1, the First Component of the Classical Pathway

Bonaparte¹,

Hair

Banthia³

et al. 2008

J Virol

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Human astroviruses (HAstVs) belong to a family of nonenveloped, icosahedral RNA viruses that cause noninflammatory gastroenteritis, predominantly in infants. Eight HAstV serotypes have been identified, with a worldwide distribution. While the HAstVs represent a significant public health concern, very little is known about the pathogenesis of and host immune response to these viruses. Here we demonstrate that HAstV type 1 (HAstV-1) virions, specifically the viral coat protein (CP), suppress the complement system, a fundamental component of the innate immune response in vertebrates. HAstV-1 virions and purified CP both suppress hemolytic complement activity. Hemolytic assays utilizing sera depleted of individual complement factors as well as adding back purified factors demonstrated that HAstV CP suppresses classical pathway activation at the first component, C1. HAstV-1 CP bound the A chain of C1q and inhibited serum complement activation, resulting in decreased C4b, iC3b, and terminal C5b-9 formation. Inhibition of complement activation was also demonstrated for HAstV serotypes 2 to 4, suggesting that this phenomenon is a general feature of these human pathogens. Since complement is a major contributor to the initiation and amplification of inflammation, the observed CP-mediated inhibition of complement activity may contribute to the lack of inflammation associated with astrovirus-induced gastroenteritis. Although diverse mechanisms of inhibition of complement activation have been described for many enveloped animal viruses, this is the first report of a nonenveloped icosahedral virus CP inhibiting classical pathway activation at C1.

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“…However, recent reports have described the factor-I-mediated degradation of C3b to iC3b that is independent of factor H on the surface of certain S. aureus strains. The overall result of this process is the decreased efficiency of bacterial killing by phagocytic neutrophils 70,71 . Although these findings are suggestive of a bacterially derived cofactor protein, current evidence suggests that S. aureus has evolved different pathways for counteracting the downstream actions of complement.…”

Section: Suppression Of Complement Amplificationmentioning

confidence: 99%

Complement evasion by human pathogens

2008

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The human immune system has developed an elaborate network of cascades for dealing with microbial intruders. Owing to its ability to rapidly recognize and eliminate microorganisms, the complement system is an essential and efficient component of this machinery. However, many pathogenic organisms have found ways to escape the attack of complement through a range of different mechanisms. Recent discoveries in this field have provided important insights into these processes on a molecular level. These vital developments could augment our knowledge of the pathology and treatment of infectious and inflammatory diseases.Evading the manifold attacks of the immune system is a key determinant for the survival of pathogens within their hosts. It is not surprising, therefore, that the coexistence and coevolution of humans and microorganisms has produced a multitude of microbial mechanisms for attenuating or escaping these attacks. As a first line of defence against pathogenic intruders, and a mediator between the innate and adaptive immune responses, the complement system is a particular focus of these evasion strategies. Although this carefully regulated cascade of enzymes, protein complexes and receptors ensures the rapid recognition and elimination of foreign structures, it also offers many sites of interference that can disrupt this balanced network of protein interactions. A detailed understanding of the individual processes and the underlying interactions on a molecular level is essential for describing the mechanisms of infectious diseases and the development of new therapies. Recent discoveries of complement-targeting proteins, the availability of complete microbial genome sequences and advances in experimental methods have propelled this area of research, and provide fascinating insights into complement attack and evasion. Many pathogens seem to have developed parallel routes for escaping complement, and several evasion principles are shared not only among members of the same genus but even among diverse organisms, such as bacteria, viruses, fungi and parasites.In this Review, we will provide a comprehensive over-view and update of the exciting recent developments in this field. After a short introduction that will discuss the diverse role of the complement system in defence, disease and infection, the emphasis will be on the functional and structural aspects of the evasion strategies of human pathogens. Rather than separating them by organism, we classify distinct and common mechanisms for all pathogens based on their mode of action. In light of recent findings, the unique evasion strategies of Staphylococcus

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Cleavage of Complement C3b to iC3b on the Surface ofStaphylococcus aureusIs Mediated by Serum Complement Factor I

Cited by 50 publications

References 23 publications

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

Human Astrovirus Coat Protein Inhibits Serum Complement Activation via C1, the First Component of the Classical Pathway

Complement evasion by human pathogens

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