On the Functional Overlap between Complement and Anti-Microbial Peptides

Zimmer, Jana; Hobkirk, James; Mohamed, Fatima; Browning, Michael; Stover, Cordula M.

doi:10.3389/fimmu.2014.00689

Cited by 15 publications

(12 citation statements)

References 159 publications

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“…Additionally, the recombinant properdin used in that study contained a histidine tag [ 42 ]. Recently several studies raised concerns about the use of proteins containing a histidine tag, since this may convey anti-microbial activity [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice

et al. 2016

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Streptococcus pneumoniae is a common cause of sepsis. Effective complement activation is an important component of host defence against invading pathogens, whilst excessive complement activation has been associated with endothelial dysfunction and organ damage. The alternative pathway amplification loop is important for the enhancement of complement activation. Factor H is a key negative regulator of the alternative pathway amplification loop and contributes to tight control of complement activation. We assessed the effect of inhibition of the alternative pathway on sepsis associated inflammation and disease severity using human factor H treatment in a clinically relevant mice model of pneumococcal sepsis. Mice were infected intravenously with live Streptococcus pneumoniae. At the first clinical signs of infection, 17 hours post-infection, mice were treated with ceftriaxone antibiotic. At the same time purified human factor H or in controls PBS was administered. Treatment with human factor H did not attenuate disease scores, serum pro-inflammatory cytokines, or vascular permeability and did not significantly affect C3 and C3a production at 26 h post-infection. Therefore, we conclude that inhibition of the alternative complement pathway by exogenous human factor H fails to attenuate inflammation and vascular leakage at a clinically relevant intervention time point in pneumococcal sepsis in mice.

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Section: Discussionmentioning

confidence: 99%

Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice

et al. 2016

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“…Furthermore, MBL2 plays a critical role in the immune system and produces primary immune response to pathogens. [Araújo et al, 2011;Zimmer et al, 2014]. In recent years, there is evidence showing that MBL2 has an important role in many diseases.…”

Section: Discussionmentioning

confidence: 99%

Association of the Risk of Dental Caries and Polymorphism of <b><i>MBL2</i></b> rs11003125 Gene in Iranian Adults

2018

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This case-control study aimed to investigate the effect of rs11003125 in dental caries. For this purpose, a total number of 404 individuals – from Fars Province in Iran – were studied. The technique of this research was the tetra-primer amplification-refractory mutation system (ARMS)-PCR. Dental caries prevalence among the 404 individuals was assessed by counting the number of decayed, missing, and filled teeth. In this research, individuals were divided into two groups: cases (n = 238) and controls (n = 166), and the peripheral blood samples were used to extract the genomic DNA. For genotyping of DNA, the tetra-primer ARMS-PCR method was conducted using specific primer pairs. While examining MBL2 rs11003125 polymorphism, we found significant differences in the genotype frequencies between the case and the control group. The pooled estimates indicated that the GG and GC genotypes of MBL2 rs11003125 polymorphism significantly increased, and therefore caries risk (OR = 2.40, 95% CI = 1.31–4.40, p = 0.004) under the dominant model. These findings suggested that polymorphism in MBL2 gene was associated with dental caries in Iranian adults. Further verification is needed with more ethnic groups and larger sample sizes to determine whether rs11003125 polymorphism is related to dental caries in other regions or not.

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“…A single low-dose treatment was enough to boost complement-activated lysis, which significantly reduced bacteremia and increased survival rates ( 178 ). We should note, however, that the recombinant properdin had histidine tag, which could influence its antimicrobial activity ( 179 ). Newly developed mouse monoclonal antibody against properdin was proved to be useful in sandwich-ELISA system to determine serum level of properdin in human samples ( 180 ).…”

Section: Components Of Ap and Lp As Potential Drug Targetsmentioning

confidence: 99%

Be on Target: Strategies of Targeting Alternative and Lectin Pathway Components in Complement-Mediated Diseases

2018

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The complement system has moved into the focus of drug development efforts in the last decade, since its inappropriate or uncontrolled activation has been recognized in many diseases. Some of them are primarily complement-mediated rare diseases, such as paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, and atypical hemolytic uremic syndrome. Complement also plays a role in various multifactorial diseases that affect millions of people worldwide, such as ischemia reperfusion injury (myocardial infarction, stroke), age-related macular degeneration, and several neurodegenerative disorders. In this review, we summarize the potential advantages of targeting various complement proteins with special emphasis on the components of the lectin (LP) and the alternative pathways (AP). The serine proteases (MASP-1/2/3, factor D, factor B), which are responsible for the activation of the cascade, are straightforward targets of inhibition, but the pattern recognition molecules (mannose-binding lectin, other collectins, and ficolins), the regulatory components (factor H, factor I, properdin), and C3 are also subjects of drug development. Recent discoveries about cross-talks between the LP and AP offer new approaches for clinical intervention. Mannan-binding lectin-associated serine proteases (MASPs) are not just responsible for LP activation, but they are also indispensable for efficient AP activation. Activated MASP-3 has recently been shown to be the enzyme that continuously supplies factor D (FD) for the AP by cleaving pro-factor D (pro-FD). In this aspect, MASP-3 emerges as a novel feasible target for the regulation of AP activity. MASP-1 was shown to be required for AP activity on various surfaces, first of all on LPS of Gram-negative bacteria.

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On the Functional Overlap between Complement and Anti-Microbial Peptides

Cited by 15 publications

References 159 publications

Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice

Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice

Association of the Risk of Dental Caries and Polymorphism of <b><i>MBL2</i></b> rs11003125 Gene in Iranian Adults

Be on Target: Strategies of Targeting Alternative and Lectin Pathway Components in Complement-Mediated Diseases

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