The Role of Properdin in C5 Convertase Activity and C5b-9 Formation in the Complement Alternative Pathway

2021 ◽  
pp. ji2100238
Author(s):  
Marloes A. H. M. Michels ◽  
Rianne J. F. Maas ◽  
Thea J. A. M. van der Velden ◽  
Nicole C. A. J. van de Kar ◽  
Lambertus P. W. J. van den Heuvel ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Complement Alternative Pathway

scholarly journals Changes in complement alternative pathway components, factor B and factor H during dengue virus infection in the AG129 mouse

2021 ◽  
Author(s):  
Sheila Cabezas-Falcon ◽  
Aidan J. Norbury ◽  
Jarrod Hulme-Jones ◽  
Sonja Klebe ◽  
Penelope Adamson ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Alternative Pathway ◽  
Severe Disease ◽  
Denv Infection ◽  
Factor H ◽  
Severe Dengue ◽  
Complement Alternative Pathway ◽  
Factor B ◽  
Dengue Disease

The complement alternative pathway (AP) is tightly regulated and changes in two important AP components, factor B (FB) and factor H (FH) are linked to severe dengue in humans. Here, a mouse model of dengue was investigated to define the changes in FB and FH and assess the utility of this model to study the role of the AP in severe dengue. Throughout the period of viremia in the AG129 IFN signalling-deficient mouse, an increase in FB and a decrease in FH was observed following dengue virus (DENV) infection, with the former only seen in a model of more severe disease associated with antibody-dependent enhancement (ADE). Terminal disease was associated with a decrease in FB and FH, with greater changes during ADE, and accompanied by increased C3 degradation consistent with complement activation. In silico analysis of NFκΒ, signal transducer and activator of transcription (STAT) and IFN-driven FB and FH promoter elements to reflect the likely impact of the lack of IFN-responses in AG129 mice, demonstrated that these elements differed markedly between human and mouse, notably with mouse FH lacking NFκΒ and key IFN-stimulated response elements (ISRE), and FB with many more NFκΒ and STAT-responsive elements than human FB. Thus, the AG129 mouse offers utility in demonstrating changes in FB and FH that, similar to humans, are associated with severe disease, but lack predicted important human-specific and IFN-dependent responses of FB and FH to DENV-infection that are likely to regulate the subtleties of the overall AP response during dengue disease in humans.

scholarly journals The Critical Role of Complement Alternative Pathway Regulator Factor H in Allergen-Induced Airway Hyperresponsiveness and Inflammation

2011 ◽  
Vol 188 (2) ◽  
pp. 661-667 ◽  
Author(s):  
Katsuyuki Takeda ◽  
Joshua M. Thurman ◽  
Stephen Tomlinson ◽  
Masakazu Okamoto ◽  
Yoshiki Shiraishi ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Alternative Pathway ◽  
Critical Role ◽  
Factor H ◽  
Complement Alternative Pathway

scholarly journals Generation and Characterization of Mouse Models of C3 Glomerulonephritis With CFI D288G and P467S Mutations

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Song ◽  
Mingchao Zhang ◽  
Xue Li ◽  
Feng Xu ◽  
Difei Zhang ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Complement Factor ◽  
C3 Glomerulonephritis ◽  
Compound Heterozygosity ◽  
Complement Alternative Pathway ◽  
Function Impairment ◽  
Specific Pathogen ◽  
Mouse Lines

C3 glomerulopathy (C3GP) is a disease entity caused by abnormality of the complement alternative pathway (AP) and characterized by C3 deposition in glomeruli. Many variations or mutations of complement factors are believed to underlie the susceptibility to C3GP, but there is a lack of experimental evidence. We have recently reported a patient with C3 glomerulonephritis (C3GN) and compound heterozygosity of two novel variations in the complement factor (CFI). Here, we generated a mouse model to mimic the CFI variations for studying pathogenicity of CFI variations in C3GN development. We used the CRISPR/Cas9 system to make mutant mouse lines that carried D288G and P467S mutations in CFI, respectively, and crossed them to generate mice with compound heterozygosity of CFI D288G and P467S. The mice were all normal in either SPF (specific pathogen free) or regular environment. When treated with lipopolysaccharides (LPS), a bacterial endotoxin that mimics infection and sepsis, the mice developed albuminuria, kidney function impairment, and C3 glomerular deposition at levels comparable with the wild-type mice. The mice with other genotypes concerning CFI D288G and P467S were also tested in parallel. Unexpectedly, we found that the D288G homozygotes all developed severe mesangial deposition of C3 in the LPS model, indicating that CFI D288G variation was involved in the C3 deposition, a key feature of C3GN. The mouse lines generated in the present study can be used to further study the role of CFI variations in C3GN development; in addition, they may be used to screen and test infections and environmental factors capable of triggering C3GN.

scholarly journals Negligible Role of Antibodies and C5 in Pregnancy Loss Associated Exclusively with C3-Dependent Mechanisms through Complement Alternative Pathway

Immunity ◽  
2003 ◽  
Vol 19 (6) ◽  
pp. 813-822 ◽  
Author(s):  
Dailing Mao ◽  
Xiaobo Wu ◽  
Christine Deppong ◽  
Lindzy D Friend ◽  
Gregory Dolecki ◽  
...  
Keyword(s):  
Pregnancy Loss ◽  
Alternative Pathway ◽  
Complement Alternative Pathway ◽  
In Pregnancy

scholarly journals New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3

2014 ◽  
Vol 34 (5) ◽  
Author(s):  
Elizabeth Rodriguez ◽  
Pavithra M. Rallapalli ◽  
Amy J. Osborne ◽  
Stephen J. Perkins
Keyword(s):  
Alternative Pathway ◽  
Factor H ◽  
Complement Factor H ◽  
Complement C3 ◽  
Complement Factor ◽  
Membrane Cofactor Protein ◽  
Complement Alternative Pathway ◽  
Factor I ◽  
Mutational Hotspots ◽  
Structural Insights

A new compilation of 324 mutations in four major proteins from the complement alternative pathway reveals mutational hotspots in factor H and complement C3, and less so in factor I and membrane cofactor protein. Their associations with function are discussed.

Acute post-streptococcal glomerulonephritis associated with prolonged hypocomplementaemia

2008 ◽  
Vol 61 (10) ◽  
pp. 1133-1135 ◽  
Author(s):  
D Payne ◽  
P Houtman ◽  
M Browning
Keyword(s):  
Renal Disease ◽  
Alternative Pathway ◽  
Complement Alternative Pathway ◽  
Pathway Activity ◽  
Post Streptococcal Glomerulonephritis

The case of a 6-year-old boy who presented with acute post-streptococcal glomerulonephritis is reported. C3 levels and complement alternative pathway activity remained low for at least 10 months after presentation, before returning to normal. There was no evidence of other renal disease. This case highlights that hypocomplementaemia in acute post-streptococcal glomerulonephritis may persist for several months, and that prolonged hypocomplementaemia does not exclude this diagnosis.

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