SEARCH · PubMed Health

Results for “Complement Factor I”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1986

Genetic expression of complement factors and alpha 1-acid glycoprotein by liver tissue during senescence.

The effect of age on several messenger RNAs coding for non-specific immune factors were determined in liver RNA isolated from 6-, 12-, 24-, 29- and 37-month-old male Fischer Rats. The levels of complement factors C3 and C4, complement protein factor B, and alpha 1-acid glycoprotein were determined by dot blot hybridization using cDNA probes. All four mRNAs increased slightly between 6 and 29 months of age. Only the mRNAs coding for complement factors C3 and C4 decreased significantly after 29 months of age. In addition, Northern blot analysis of the RNA preparations showed that the size of the four mRNA species did not change with increasing age. There was no evidence for age-related changes in the post-transcriptional processing or degradation of the mRNA species coding for complement factors C3 and C4, complement protein factor B, and alpha 1-acid glycoprotein.

Age Factors↗

PubMed2000

Activated microglial cells and complement factors are unrelated to cortical Lewy bodies.

Inflammatory mechanisms have been demonstrated in Alzheimer's disease (AD) but their presence in other neurodegenerative disorders is not well documented. Complement factors and activated microglia have been reported in the substantia nigra of Parkinson's disease (PD). In the present study we investigated the cingulate gyrus of 25 autopsied patients with clinically and neuropathologically well-documented PD, with or without dementia, for the presence of (activated) microglial cells and their relation with Lewy body (LB)-bearing neurons. In addition, we studied the presence of complement factors in LBs. Of the 25 patient, 15 were clinically demented, fulfilling criteria for dementia with LBs (DLB); 7 also fulfilled CERAD morphological criteria for probable or definite Alzheimer type of dementia. Microglia clustering was seen around congophilic plaques with or without tau pathology. Microglial cells were not associated with LB-bearing neurons or noncongophilic plaques. The cortex of DLB patients without AD plaques did not show more microglial cells than the cortex of non-demented controls. The number of microglia was the lowest in young control patients who died immediately after trauma. Complement factor C3d was occasionally seen in diffusely ubiquinated neurons but late complement factors were not detected in these neurons. Double staining for complement and alpha-synuclein was negative, suggesting the absence of complement in LBs. In contrast, AD plaques in the same sections showed complement factors C3c, C3d, C1q and C5-9. In conclusion, we have found no evidence that inflammatory mechanism are involved in LB formation in cerebral cortex.

Aged↗

PubMed1989

Adipsin and complement factor D activity: an immune-related defect in obesity.

Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder. Recombinant mouse adipsin was purified and its biochemical and enzymatic properties were studied in order to elucidate the function of this protein. Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3. Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis. Decreased (58 to 80 percent) complement factor D activity, relative to lean controls, was observed as a common feature of several experimental models of obesity, including the ob/ob, db/db, and monosodium glutamate (MSG)-injected mouse and the fa/fa rat. These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo.

Adipose Tissue↗

PubMed2006

[Non-ionic iodinated dimeric versus monomeric X-ray contrast media: effects on complement factors in vivo].

PURPOSE: To survey contrast media (CM)-induced alterations of complement factors. MATERIAL AND METHODS: In 31 adult patients, who received either an iotrolan (n = 19) or iopromide (n = 12) i. v. injection for CT examination, complement factors C1 q, C3, C4, C5 a, and C1-esterase inhibitor in serum/plasma samples were analyzed. The samples were obtained prior to and 5 min., 30 min., 1 hr., 6 hrs. and 24 hrs. after CM injection. RESULTS: 5 patients (16.1 %) developed a CM reaction. 4 of these were patients who received iotrolan. Other than minimal data, we neither found a significant influence of the CM on complement activation nor a difference between the analyzed CM. In detail, 5 min. after CM administration, we found the tendency to be for the values to decrease and then to return to the basic value. The changes induced by iotrolan were more pronounced than those induced by iopromide; nevertheless the differences were not statistically significant. A more pronounced decrease of C3 and C4 after iotrolan injection indicates the activation of the classic way, while this could not been observed after iopromide injection. One patient who experienced an unwanted reaction towards iotrolan showed shifts of C1 q, C1 INH, C3 and C4. CONCLUSION: The presented data shows different influences of CM injection on the analyzed complement factors after 5 min. that were commonly no longer present 30 min. after CM injection. The dimeric iotrolan induced a significantly increased frequency of unwanted CM reactions than the monomeric iopromide. The question of whether iotrolan is possibly able to activate the classic way of the complement cascade should be analyzed in the future in a greater patient group.

Adult↗

PubMed1993

Effects of sulphated polyanions on functions of complement factor H.

Heparin and two dextran sulphate preparations with a low or high average molecular mass (M(r) 5000 and 5 x 10(5), respectively) enhanced binding of radioactively labelled complement factor H to the complement protein C3b, coupled to Sepharose 4B, maximally 2.5-4-fold within a polyanion concn range of 12.5-400 micrograms/ml. Despite this, heparin or low molecular mass dextran sulphate had no effect on the activity of H as a cofactor of complement factor I, when C3b bound to Sepharose 4B was used as a substrate, and high molecular mass dextran sulphate inhibited. Heparin or low molecular mass dextran sulphate had also no effect on the decay-accelerating activity of factor H on the alternative pathway C3 convertase, C3b,Bb, and high molecular mass dextran sulphate inhibited this activity, too, regardless of whether Sepharose 4B or sheep erythrocytes were used as carriers of C3b,Bb. These results suggest strongly that fluid phase heparin or dextran sulphate do not inhibit activation of the alternative pathway of complement by augmenting functions of H.

Complement C3b↗

PubMed1988

Allelic variants for complement factors C3, C4, and B in acute necrotizing ulcerative gingivitis.

Impaired immune defense mechanisms and genetic factors appear to play a role in susceptibility to acute necrotizing ulcerative gingivitis (ANUG). Therefore, possible etiological mechanisms might involve genes at the Major Histocompatibility Complex, which include the complement factor loci. We have tested for a possible association between certain complement factor alleles and ANUG using a case-control study design. Specific alleles at complement factors C3 and C4, and properdin factor B (Bf) loci were determined indirectly by high voltage agarose gel electrophoresis in 58 subjects with a history of ANUG and in 58 age-sex-matched healthy controls. The highest relative risk of ANUG, as obtained by conditional logistic regression, for alleles at the C3 locus was 1.9 (90% confidence limits 0.8 to 4.8; p = 0.229) for C3*F-positive individuals. The highest relative risk for alleles at the C4 locus was 2.6 (0.5 to 14.9; p = 0.358) for C4A*3-positive individuals. There was no evidence for an association between Bf allotype and risk of ANUG, with a relative risk of 1.2 for Bf*F- and relative risk of 1.0 for B*S-positive individuals. None of our estimates was statistically significant. We conclude, therefore, that it is unlikely that there is any association between complement factor gene haplotype and susceptibility to ANUG.

Acute Disease↗

PubMed1985

Complement factor C4 in schizophrenia.

The complement factor C4 was studied in 165 schizophrenic patients and in 330 controls. A highly significant increase in the frequency of C4B deficiency (BQO) was found among the schizophrenic patients compared with controls (p less than 0.0005).

Complement C4↗

PubMed2001

Immunoglobulin classes, complement factors and circulating immune complexes in chronic sinusitis patients.

Serum concentrations of immunoglobulin classes (IgG, IgA and IgM), complement factor B (FB), 4th complement factor (C4) and circulating immune complexes (CIC) were determined in 34 Nigerians with chronic sinusitis and 37 apparently healthy age and sex matched controls by single radial immunodiffusion and polyethylene glycol precipitation methods, respectively. The mean serum IgG, IgA, C4, FB and CIC were significantly reduced in chronic sinusitis patients compared with the controls. The mean serum levels of IgG, IgM, C4 and FB were higher in male chronic sinusitis patients compared with female patients. In contrast the mean serum level of IgA was significantly reduced in chronic sinusitis patients. Only IgG and IgA showed significant correlation with the duration of chronic sinusitis. These findings in Nigerian patients suggest immuno-deficiency as one of the causes of chronic sinusitis in Nigerians, therefore routine serum immunoglobulin evaluation is recommended and if found deficient immunoglobulin replacement therapy is advocated for the treatment of such chronic sinusitis.

Adolescent↗

PubMed1986

Partial characterization of human complement factor H by protein and cDNA sequencing: homology with other complement and non-complement proteins.

Factor H, a control protein of the human complement system, is closely related in functional activity to two other complement control proteins, C4b-binding protein (C4bp) and complement receptor type 1 (CR1). C4bp is known to have an unusual primary structure consisting of eight homologous units each about 60 amino acids long. Such units also occur in the N-terminal regions of the complement proteins C2 and factor B, and in the non-complement serum glycoprotein beta 2I. Amino acid sequencing, and sequencing of a factor H cDNA clone, show that factor H also contains internal repeating units, and is homologous to the proteins listed above.

Amino Acid Sequence↗

PubMed2004

Glomerular deposition and urinary excretion of complement factor H in idiopathic membranous nephropathy.

BACKGROUND/AIMS: The complement system plays an important role in the pathogenesis of membranous nephropathy (MN). In order to elucidate the regulatory mechanism of complement activation, we demonstrated glomerular deposition and urinary excretion of complement factor H, which controls the alternative pathway and the amplification loop at the C3 step, in patients with idiopathic MN. METHODS: Renal biopsy specimens from 20 patients with idiopathic MN were studied immunohistochemically using monoclonal antibodies against complement components including factor H. SDS-PAGE and Western blotting analysis of urine samples were performed, and the urinary excretion of factor H and C5b-9 were measured by quantitative sandwich ELISA. RESULTS: Intense glomerular deposition of factor H was observed with C3b.C3c and C5b-9 at an early stage of the disease. Factor H was detected in Western blots of urine samples, but factor H-like protein 1 (FHL-1) was not. The mean level of urinary factor H was elevated (86.30 +/- 21.93 U/mg urinary creatinine) in comparison to that of normal controls (4.76 +/- 1.03 U/mg urinary creatinine). Urinary factor H level exhibited no correlation with clinical parameters; however, a negative correlation was found between urinary C5b-9/factor H and creatinine clearance (r = 0.662, p < 0.01). CONCLUSION: The source of glomerular and urinary factor H is supposedly a 150-kD protein. There was no evidence to suggest that FHL-1 is synthesized at the site of inflammation. The urinary C5b-9 to urinary factor H ratio is indicative of the degree of ongoing complement activation in the glomeruli and complement-mediated renal injury. These findings suggest that factor H contributes to the control mechanism of in situ complement activation and prevents renal damage in idiopathic MN.

Alternative Splicing↗

PubMed1989

Regulation of human and murine complement: comparison of 5' structural and functional elements regulating human and murine complement factor B gene expression.

The serine protease complement factor B (Bf), an acute phase plasma protein, is a component of the alternative pathway of complement activation. Previous studies revealed that several cytokines including IFN-gamma and IL-1 are involved in mediating acute phase Bf expression. To determine the molecular details of Bf expression we isolated, sequenced and characterized the 5' flanking regions of the human and murine Bf genes. In both species the Bf transcriptional start site in liver was located less than 400 bp 3' to the polyadenylation site of the upstream C2 gene. This upstream intergenic region contained greater than 65% nucleotide homology between species. Within this region, an IRS and three heat shock consensus elements were found in the murine sequence in an identical position to that of the human. To examine the functional details of Bf expression, a series of mouse and human Bf promoter-chloramphenicol acetyltransferase (CAT) chimeric gene constructs were transfected into mouse L or human HepG2 cells. Analysis of expression of these fusion gene constructs revealed that 1) cis-acting DNA sequences identified, at least in part, in the 3' untranslated region of the C2 gene (within the 400 bp upstream of the Bf cap site) mediate responsiveness to IL-1 and IFN-gamma, 2) the responsiveness to each mediator appears to be conferred by separate upstream regions similar in position and homologous in man and mouse, and 3) the IL-1 responsive region in both species appears to have the characteristics of an enhancer element. The results of this analysis suggest a selective pressure to conserve the intergenic sequence between C2 and Bf genes and that further studies of these sequences will be useful in elucidating mechanisms controlling the acute phase response.

Animals↗

PubMed2006

A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: the Rotterdam Study.

OBJECTIVES: This study was designed to investigate the association between a common polymorphism (Tyr402His, rs1061170) in the complement factor H (CFH) gene and risk of coronary heart disease. BACKGROUND: The evidence that inflammation is an important mechanism in atherogenesis is growing. C-reactive protein (CRP), complement factors, and complement regulatory factors have all been linked to coronary heart disease. The CFH gene is an important regulator of the alternative complement cascade. We investigated its association with coronary heart disease. METHODS: The study was embedded in the Rotterdam Study, a prospective population-based study among men and women aged 55 years and over. A total of 5,520 participants without history of coronary heart disease was genotyped for the Tyr402His polymorphism of the CFH gene. Cox proportional hazards analysis was used to determine risk of myocardial infarction for Tyr402His genotypes. RESULTS: Mean age among participants was 69.5 years (SD 9.1 years). The overall frequency of the His allele was 36%; genotype frequencies were 41%, 45%, and 14% for TyrTyr, TyrHis, and HisHis, respectively. During a mean follow-up period of 8.4 years, 226 myocardial infarctions occurred. After adjustment for age, gender, established cardiovascular risk factors, and CRP level, HisHis homozygotes had a hazard ratio of 1.77 (95% confidence interval 1.23 to 2.55) for myocardial infarction. Total cholesterol level, diabetes mellitus, and smoking modified the effect. The Tyr402His polymorphism was not associated with established cardiovascular risk factors or CRP level. CONCLUSIONS: Our data suggest that the CFH gene determines susceptibility to myocardial infarction. This finding underscores the importance of the alternative complement system in cardiovascular disease.

Aged↗

PubMed2006

The simple design of complement factor H: Looks can be deceiving.

The complement system is a powerful component of innate immunity which recognizes and facilitates the elimination of pathogens and unwanted host material. Since complement can also lead to host tissue injury and inflammation, strict regulation of its activation is important. One of the key regulators is complement factor H (CFH), a protein with an ever-expanding list of relevant functions. Inherited mutations in CFH can account for membranoproliferative glomerulonephritis (MPGN) type II, atypical hemolytic uremic syndrome, and age-related macular degeneration. The former can be associated with excessive systemic complement activation from dysfunctional CFH, while the latter two are associated with mutations affecting the ability of CFH to bind to anionic surfaces such as on endothelial cells and glomerular and retinal capillary walls. Mice with targeted deletion of CFH can spontaneously develop MPGN and have increased susceptibility to models of GN. In the rodent, CFH on platelets functions as the immune adherence receptor, analogous to CR1 on primate erythrocytes. In mice, platelets lacking CFH are unable to effectively clear immune complexes which results in their accumulation in glomeruli. The same switch also appears to be true in the rodent podocyte where CFH is present in place of CR1 in human podocytes. Thus, CFH has a variety of functions which can affect the diverse roles the complement system plays in health and disease.

Animals↗

PubMed1989

C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis.

In a series of patients with acute pancreatitis we have studied complement factors, antiproteases (alpha 2-macroglobulin and alpha 1-antiprotease) and C-reactive protein to determine the value of their sequential measurement in the prediction of outcome relative to clinical assessment and current multiple factor scoring systems. Complement factors were unhelpful in predicting the severity of an attack. alpha 2-Macroglobulin levels were significantly lower in complicated attacks during days 3-8 and alpha 1-antiprotease levels were significantly higher during days 4-8. C-reactive protein concentrations showed the best discrimination between mild and complicated attacks, levels rising higher and persisting for longer in complicated attacks; these differences were highly significant from day 2 (the morning after admission) to day 8. The concentrations providing the best discrimination were found to be greater than or equal to 210 mg/l for the peak C-reactive protein (on the second, third or fourth day) and greater than or equal to 120 mg/l for the C-reactive protein at the end of the first week. Analysis demonstrated both the peak or seventh-day C-reactive protein concentration to be of similar accuracy to either the Ranson or Glasgow multiple factor scoring systems and slightly better for attacks associated with gallstones. The C-reactive protein assay is simple, quick to perform, provides useful clinical information and is more likely to be of value and to be adopted into routine clinical practice than multiple factor scoring systems.

Acute Disease↗

PubMed1989

Hereditary, complete deficiency of complement factor H associated with recurrent meningococcal disease.

Complement factor H (beta-1H globulin) is an important regulatory protein which inhibits the spontaneous complement activation via the alternative pathway. We describe a 15-year-old girl without any detectable factor H in plasma. She has had two episodes of meningococcal disease, but is otherwise completely healthy. Secondary to the factor-H deficiency, the levels of factor B, properdin, C3, and C5-C9 were strongly reduced due to spontaneous in vivo activation of the alternative complement pathway. Plasma C3dg was strongly elevated in spite of the factor-H deficiency; apparently erythrocyte CR1 substitutes for factor H in C3 degradation. Neither C3 nor complement lesions were demonstrable on her erythrocytes which did, however, show increased, spontaneous haemolysis in vitro in citrate plasma, but not in serum. The patient is a single child and her parents, who are unrelated and healthy, had half-normal levels of factor H. This reduction of factor H is sufficient to cause increased, spontaneous activation of the alternative pathway.

Antibodies, Bacterial↗

PubMed2006

Compstatin inhibits complement activation by binding to the beta-chain of complement factor 3.

Compstatin is a peptidic complement inhibitor that prevents the cleavage of complement factor 3 (C3) by C3 convertase. Compstatin differs from other C3-regulatory proteins, such as complement receptor (CR) 1 and decay-accelerating factor (DAF), in that it binds native as well as activated C3 fragments and acts through mechanisms that do not involve the destabilization of the C3 convertase or the accelerated degradation of C3b. Compstatin's activity most likely relies on its affinity for native C3 and the conformational change that results upon binding with C3. Although the intermolecular interactions between compstatin and C3 have been studied, the identity of the targeted region on C3 is still elusive. To address this issue, we synthesized a photo-crosslinking compstatin analog and used it to probe C3 for sites of interaction. We identified a 40-kDa region at the C-terminus of the beta-chain of C3 that included the binding site of the compstatin analog. The specificity of the binding was confirmed by inhibition studies, which showed reduced crosslinking signal after pre-incubation of C3 with compstatin but not with various inactive analogs. Binding studies performed with a recombinant homolog of the 40-kDa region confirmed these findings. Five smaller recombinant proteins corresponding to various overlapping regions of the 40-kDa fragment did not bind compstatin, suggesting that a proper protein conformation, only found in larger fragments, is required for compstatin binding. The identified region on the beta-chain has, thus far, not been implicated in C3 cleavage or interactions with other proteins. Therefore, further research on this part of the C3 molecule may have implications for studies on the regulation of C3 cleavage, as well as for complement-based drug design.

Binding Sites↗

PubMed2003

Nickel and cobalt activate complement factor C3 faster than magnesium.

We have found that incubation of heparin plasma with Ni(2+) or Co(2+) at concentrations below 100 microM can stimulate the conversion of complement factor C3 to C3b faster than magnesium, which is the natural cofactor in the alternative complement activation. This conversion was monitored by light absorbance measurement after separation by isotachophoresis, immunofixation and protein staining. The generation of C3b stimulated by these metals (<0.5 mM) proceeds up to about four times faster than the stimulation by Mg(2+). Half of total C3 in the incubation media was converted by Ni(2+) or Co(2+) at 0.5 mM after 20 min at 37 degrees C. Increasing Ni(2+) concentrations over 0.5 mM decreased the C3 conversion rate. Activation of C3 stimulated by Ni(2+), Co(2+) and Mg(2+) was concomitant with the conversion of complement factor B to Bb, but complement factor C4 was not affected by the activation. The conversion of B to Bb was monitored after separation by isotachophoresis and immunoblotting. Other divalent metal ions tested, namely Ca(2+), Ba(2+), Cu(2+) and Zn(2+), did not stimulate the complement cascade. We postulate that the increased rate of C3-fragment production induced by nickel or cobalt ions is central for the immunotoxicity of these metals.

Animals↗

PubMed1984

Isolation of two molecular populations of human complement factor H by hydrophobic affinity chromatography.

Human complement factor H was prepared in highly purified form from fresh serum by euglobulin precipitation, DEAE-Sephacel chromatography and Sephacryl S-300 gel filtration. This preparation allowed the recovery of 37% of the initial factor H. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed that factor H was homogeneous both in reduced and non-reduced media and exhibited a molecular mass of 150 kDa. Charge-shift experiments clearly showed the presence of hydrophobic sites in the factor H molecule. Charge shifts were observed with two detergent systems (Triton/sodium deoxycholate and Triton/cetyltrimethylammonium bromide). Factor H was able to bind to phenyl-Sepharose. This property allowed us to study two populations of factor H. These two populations exhibited the same physicochemical parameters, but revealed differences in their ability to aggregate in low- and iso-ionic-strength media. The molecular basis and biological significance of this heterogeneity are discussed.

Amino Acid Sequence↗