Deficiencies of the Complement System

Frank, Michael M.; Sullivan, Kathleen E.

doi:10.1016/b978-0-12-405546-9.00038-8

Cited by 8 publications

(4 citation statements)

References 228 publications

(311 reference statements)

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“…CO3 modulates the complement cascade activation and is a biomarker of inflammatory response to biomaterials [34]. CFAD is exclusive to the alternative pathway of the complement system; it is crucial for the cleavage of the lysine-arginine bond in the complement factor B [35,36]. Many of the complement proteins are activated in the host at the site of inflammation, forming convertases (namely C3 and C5 convertases) as the end-product.…”

Section: Discussionmentioning

confidence: 99%

Complement proteins regulating macrophage polarisation on biomaterials

Araújo‐Gomes

Romero‐Gavilán

Zhang

et al. 2019

Colloids and Surfaces B: Biointerfaces

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One of the events occurring when a biomaterial is implanted in an host is the protein deposition onto its surface, which might regulate cell responses. When a biomaterial displays a compromised biocompatibility, distinct complement pathways can be activated to produce a foreign body reaction. In this article, we have designed different types of biomaterial surfaces to study the inflammation process. Here, we used different concentrations of (3-glycidoxypropyl)-trimethoxysilane (GPTMS), an organicallymodified alkoxysilane as a precursor for the synthesis of various types of sol-gel materials functionalizing coatings for titanium implants to regulate biological responses. Our results showed that increasing GPTMS concentration slightly enhanced the osteogenic potential of MC3T3-E1 cells in vitro, which seems linked to upregulation of TGF-β expression. Moreover, greater GPTMS surface concentrations induced greater secretion of TNF-α and IL-10 on RAW 264.7 macrophages. When implanted into rabbit tibia, osseointegration decreased with higher GPTMS concentrations. Interestingly, higher deposition of complement-related proteins C-reactive protein (CRP) and ficolin-2 (FCN2), two main activators of distinct complement pathways, was observed. Taking all together, inflammatory potential increase seems to be GPTMS concentrationdependent. Our results show that a greater adsorption of complement proteins can condition macrophage polarization.

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Section: Discussionmentioning

confidence: 99%

Complement proteins regulating macrophage polarisation on biomaterials

Araújo‐Gomes

Romero‐Gavilán

Zhang

et al. 2019

Colloids and Surfaces B: Biointerfaces

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“…The C1q subunit of the C1 complex consists of three highly homologous proteins: C1qA, C1qB, and C1qC [ 32 ]. C1q is formed by 18 polypeptide chains in total: Six A-chains, six B-chains, and six C-chains [ 19 ] ( Figure 1 b).…”

Section: Complement Protein C1q: the Initiating Protein Of The Clamentioning

confidence: 99%

Schizophrenia: Complement Cleaning or Killing

Hogenaar

Bokhoven

2021

Genes

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Schizophrenia is a psychiatric disorder with a typical onset occurring during adolescence or young adulthood. The heterogeneity of the disorder complicates our understanding of the pathophysiology. Reduced cortical synaptic densities are commonly observed in schizophrenia and suggest a role for excessive synaptic elimination. A major pathway hypothesised to eliminate synapses during postnatal development is the complement system. This review provides an overview of genetic and functional evidence found for the individual players of the classical complement pathway. In addition, the consequences of the absence of complement proteins, in the form of complement protein deficiencies in humans, are taken into consideration. The collective data provide strong evidence for excessive pruning by the classical complement pathway, contributing to cognitive impairment in schizophrenia. In future studies, it will be important to assess the magnitude of the contribution of complement overactivity to the occurrence and prevalence of phenotypic features in schizophrenia. In addition, more insight is required for the exact mechanisms by which the complement system causes excessive pruning, such as the suggested involvement of microglial engulfment and degradation of synapses. Ultimately, this knowledge is a prerequisite for the development of therapeutic interventions for selective groups of schizophrenia patients.

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“…DAF is a glycophosphatidylinositol anchored membrane protein broadly found on most cells and tissues, including erythrocytes, lymphocytes, granulocytes, endothelium and epithelium ( 10 ), and the presence of soluble DAF has also been reported in saliva, urine, plasma, tears and synovial fluid ( 11 ). In addition to being a complement regulatory protein, DAF binds CD97, a G protein coupled receptor ( 12 13 ).…”

Section: Introductionmentioning

confidence: 99%

Decay-Accelerating Factor Differentially Associates With Complement-Mediated Damage in Synovium After Meniscus Tear as Compared to Anterior Cruciate Ligament Injury

Holers,

Frank,

Zuscik

et al. 2024

Immune Netw

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We have reported that anterior cruciate ligament (ACL) injury leads to the differential dysregulation of the complement system in the synovium as compared to meniscus tear (MT) and proposed this as a mechanism for a greater post-injury prevalence of post traumatic osteoarthritis (PTOA). To explore additional roles of complement proteins and regulators, we determined the presence of decay-accelerating factor (DAF), C5b, and membrane attack complexes (MACs, C5b-9) in discarded surgical synovial tissue (DSST) collected during arthroscopic ACL reconstructive surgery, MT-related meniscectomy, osteoarthritis (OA)-related knee replacement surgery and normal controls. Multiplexed immunohistochemistry was used to detect and quantify complement proteins. To explore the involvement of body mass index (BMI), after these 2 injuries, we examined correlations among DAF, C5b, MAC and BMI. Using these approaches, we found that synovial cells after ACL injury expressed a significantly lower level of DAF as compared to MT (p<0.049). In contrast, C5b staining synovial cells were significantly higher after ACL injury (p<0.0009) and in OA DSST (p<0.039) compared to MT. Interestingly, there were significantly positive correlations between DAF & C5b (r=0.75, p<0.018) and DAF & C5b (r=0.64 p<0.022) after ACL injury and MT, respectively. The data support that DAF, which should normally dampen C5b deposition due to its regulatory activities on C3/C5 convertases, does not appear to exhibit that function in inflamed synovia following either ACL injury or MT. Ineffective DAF regulation may be an additional mechanism by which relatively uncontrolled complement activation damages tissue in these injury states.

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Deficiencies of the Complement System

Cited by 8 publications

References 228 publications

Complement proteins regulating macrophage polarisation on biomaterials

Complement proteins regulating macrophage polarisation on biomaterials

Schizophrenia: Complement Cleaning or Killing

Decay-Accelerating Factor Differentially Associates With Complement-Mediated Damage in Synovium After Meniscus Tear as Compared to Anterior Cruciate Ligament Injury

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