Search results for "Complement Factor H"

Research on complement: old issues revisited and a novel sphere of influence

2003

Immunology in recent years has taken a somewhat surprising turn, expressed by a renewed interest in innate immunity. Especially intriguing is the regulatory role exerted by the innate components on the adaptive response, with Toll receptors and complement components being the most investigated. This function has been firmly established for complement protein CR2 (CD21) as part of the BCR co-receptor CD19/CD21/CD81. New findings are now providing a broader picture of complement and its tuning of the immune response; for example, complement proteins have been implicated in the control of T-cell-mediated responses. We will review some of these data here and summarize new discoveries in areas o…

Activation of the alternative pathway of complement: efficient fluid-phase amplification by blockade of the regulatory complement protein β1H through…

1981

Current concepts of activation of the alternative pathway of complement (APC) focus on the central role of an amplification mechanism triggered by C3b which is covalently bound to the surfact of activating substances. Using sulfated polyanions as model substances, an efficient fluid-phase activation of complement is demonstrated in contrast to solid-phase activation. It is shown that particulate high-molecular weight sulfated polyanions are capable of reversible binding the guinea pig and human regulatory protein beta1H. This fixation leads to an extensive activation of C3 and factor B because the regulatory function of beta1H is blocked in the fluid-phase C3b-dependent amplification system…

Cyclic AMP-mediated upregulation of the expression of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the level of…

2004

The expression level of neuronal nitric oxide synthase (nNOS) can vary depending on the (patho)physiological conditions. Here we document a marked induction of nNOS mRNA, protein, and total NO production in response to dibutyryl cyclic AMP (db-cAMP) in human A673 neuroepithelial cells. However, the upregulation of nNOS was associated with a decreased level of production of bioactive NO and by an increase in the level of generation of reactive oxygen species (ROS). ROS production could be prevented by the NOS inhibitor L-NAME, suggesting nNOS itself is involved in ROS generation. Sepiapterin supplementation of db-cAMP-treated A673 cells could restore full bioactive NO production, most likely…

Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Dise…

2018

The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the U.S and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H. To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds factor H to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because factor H-binding cloaks potentially pro…

Genetic prediction of ICU hospitalization and mortality in COVID‐19 patients using artificial neural networks

2021

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, …

Genetic justification of severe COVID-19 using a rigorous algorithm

2021

Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID-19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (…

Importance of Factors H and I for the Adherence of C3b-Coated Erythrocytes to Cells

1983

Abstract The role of cell membrane-associated human factor H for the binding of cell-bound Cab to complement receptor-carrying (CR + ) cells was investigated. Pretreatment of CR + cells with antibodies to factor H inhibited the adherence of Cab-coated red cells to human tonsil lymphocytes (TL) and peripheral blood monocytes (Mo). The Cab receptor reactivity of human polymorphonuclear leucocytes (PMN) was not influenced and the one of Raji lymphoblastoid cells only slightly influenced; iC3b and Cad receptor reactivity was in no case affected. When diisopropylfluorophosphate (DFP) in a concentration of 0.1 mM was present during pretreatment of the CR + cells with anti H, the antibodies gained…

Role of β1H for the binding of C3b-coated particles to human lymphoid and phagocytic cells

1981

Coating of EAC14oxy23b with highly purified human serum beta 1H globulin (beta 1H) led to acceleration of rosette formation with human peripheral blood lymphocytes (PBL), tonsil lymphocytes, B lymphoblastoid (Raji) cells, granulocytes and monocytes. This reaction was discernible from C3bi-dependent rosette formation. Enhancement of rosette formation of C3b cells by beta 1H was most effective at limiting amounts of C3 per EAC14oxy23b. The beta 1H effect was not due to trace contamination with C3b inactivator. beta 1H-dependent rosette formation with the various lymphoid and phagocytic cells could be suppressed by the F(ab')2 fragment of anti-beta 1H suggesting beta 1H-mediated binding of bet…

Molecular basis for factor H and FHL-1 deficiency in an Italian family

2000

Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia

2013

Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare M…