Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,549 records · Page 86Linked to original sources
PubMed1979

Lethal effect of complement and lysozyme on polymyxin-treated, serum-resistant gram-negative bacilli.

When genetically serum-resistant Escherichia coli, Klebsiella pneumoniae, and Citrobacter freundii, but not Pseudomonas aeruginosa or Proteus mirabilis, were exposed to polymyxin B, they became susceptible to the bactericidal action of normal human and rabbit sera. In constrast, beta-lactam and aminoglycoside antibiotics did not render any serum-resistant bacteria serum-sensitive. Synergy between polymyxin B and the serum bactericidal system could be demonstrated by the addition of polymyxin B to bacteria in vitro, as well as to bacilli in serum from rabbits injected with the antibiotic. Polymyxin B-treated bacteria were killed by normal, lysozyme-depleted, C2-deficient, and hypogammaglobulinemic sera, but not by heated or C6-deficient sera. These findings indicate that polymyxin B-treated bacteria can be killed via the alternative complement pathway. However, C3 and C3b were detected on the surface of serum-resistant E. coli, regardless of whether the bacteria had been treated with polymyxin B. This observation suggests that a change in susceptibility to the alternative complement pathway was not the only explanation for the acquired serum sensitivity. Polymyxin B may also affect a step in the complement sequence beyond the activation of C3, a step that is apparently blocked in serum-resistant gram-negative bacteria.

Animals↗
PubMed1984

Solubilization of immune complexes in complement factor deficient sera and the influence of temperature, ionic strength and divalent cations on the solubilization reaction.

The complement-mediated solubilization (CMS) of immune complexes (IC) and the initial kinetics (IKS) of this reaction in human sera depleted of or deficient in C2, C3, C8, factors B, P and I were investigated. Sera depleted of B or P and those lacking native C3 or factor I showed virtually no CMS whereas the IKS and CMS capacity of a C8-deficient serum were within the reference range. The IKS of a C2-deficient serum was markedly retarded while the CMS capacity was normal. Addition of C2 normalized the kinetics of the reaction. There was a good correlation between the kinetics of CMS determined by a radioassay and kinetic data for the binding of C3b to preformed immune complexes. The CMS capacity reached maximum at 39-41 degrees C and at an ionic strength of approximately 0.20 mu. Selective chelation of Mg2+ completely abolished the CMS of IC. Maximal CMS was observed at Mg2+ concentration of about 2mM. Chelation of Ca2+ in serum by Mg2+-ethylene glycol tetraacetic acid reduced the CMS capacity by up to 50% and the IKS was markedly retarded. Varying the Zn2+ or Mn2+ ion concentrations in serum influenced neither the IKS nor the CMS capacity.

Antigen-Antibody Complex↗
PubMed1973

Interactions of the classical and alternate complement pathway with endotoxin lipopolysaccharide. Effect on platelets and blood coagulation.

The contributions of the classical and alternate pathways of complement activation to the biological effects of endotoxin have been examined in the guinea pig, with particular reference to thrombocytopenia, leukopenia, and the development of the hypercoagulable state. Injection of endotoxin into normal guinea pigs led to a 95% fall in the level of circulating platelets within 15 min as well as a fall in circulating granulocytes. C4-deficient guinea pigs, known to have a complete block in the activity of the classical complement pathway, but with the alternate pathway intact, sustained no fall in platelets. The development of granulocytopenia proceeded normally. Endotoxin did activate the alternate complement pathway in C4D guinea pigs, as evidenced by the fall in C3-9 titers. With restoration of serum C4 levels, endotoxin-induced thrombocytopenia was observed in C4D animals. Thus, function of the classical complement pathway was an absolute requirement for the development of thrombocytopenia. Experiments performed in cobra venom factor (CVF)-treated normal guinea pigs, with normal levels of C1, C4, and C2, but with less than 1% of serum C3-9 demonstrated the importance of the late components in the development of thrombocytopenia but not leukopenia.C4-deficient guinea pigs had normal clotting times demonstrating that C4 was not required for normal clotting. In addition, development of the hypercoagulable state, evidenced by a marked shortening of the clotting time, was not observed on injection of endotoxin into C4D animals. Therefore, development of the hypercoagulable state paralleled the development of thrombocytopenia and required function of the classical complement pathway. Again, the importance of the late components of complement was emphasized by the failure of CVF-treated normal animals to develop hypercoagulability. These results demonstrate that endotoxin is capable of activating both the classical and alternate complement pathways in guinea pigs but that function of the classical pathway is an absolute requirement for the development of thrombocytopenia and the hypercoagulable state.

Animals↗
PubMed1986

alpha-DNA. I. Synthesis, characterization by high field 1H-NMR, and base-pairing properties of the unnatural hexadeoxyribonucleotide alpha-[d(CpCpTpTpCpC)] with its complement beta-[d(GpGpApApGpG)].

The novel deoxyribonucleotide alpha-[d(CpCpTpTpCpC)] and its complement beta-[d(GpGpApApGpG)] were synthesized by the phosphotriester method. 1H-NMR-NOE examination of the alpha-hexamer revealed that the cytosine and thymine bases appear to adopt anti conformations in this strand. In addition the deoxyribose of the thymidine moieties may adopt average conformations approximating to C3'-endo while the cytidine furanose groups are close to C2'-endo conformations. Both hyperchromicity in thermal melting and detection of base paired imino protons in 1H-NMR studies in H2O provide evidence for the annealing of alpha-d[CCTTCC] with its complement beta-d[GGAAGG] in potassium phosphate buffer pH 7.1 containing 10 mM magnesium chloride. Under these conditions thermal melting begins at 38 degrees C and its complete at approximately 45 degrees C. NOE experiments do not permit a decision on the polarity of annealing (predicted to be parallel) for this particular pair of sequences.

Chemical Phenomena↗
PubMed1974

Elastase of Pseudomonas aeruginosa: inactivation of complement components and complement-derived chemotactic and phagocytic factors.

A purified elastase from Pseudomonas aeruginosa was highly destructive for fluid-phase and cell-bound C1 and C3 and fluid-phase C5, C8, and C9. Inactivation of C4, C2, C6, and C7 by the enzyme varied from 0 to 67%. Low concentrations of elastase generated, then inactivated, a chemotactic factor from human C5 but not from C3. Higher enzyme concentrations inactivated the C5 chemotactic activity at a faster rate. Elastase treatment of sensitized pseudomonads containing cell-bound C3 reduced the phagocytic indexes of polymorphonuclear leukocytes. The data support the proposed chemopathogenic role of the elastase in generation of the characteristic non-inflammatory Pseudomonas vasculitis.

Animals↗
PubMed1999

Angioedema due to acquired C1-esterase inhibitor deficiency in a patient with Helicobacter pylori infection.

The first component of the classical pathway of the complement system, C1 is regulated by a serum protein, the C1-esterase inhibitor (C1-INH). Deficiency of this protein leads to the release of vasoactive mediators (C2 kinin and bradykinin) that increase vascular permeability and can induce edema formation in subcutaneous and submucosal tissues. The genetic variant of C1-INH deficiency is inherited as an autosomal dominant trait and causes hereditary angioneurotic edema. The acquired form of C1-INH deficiency is characterized by similar manifestations and can occur in association with lymphoproliferative diseases, malignancy, immune disorders, and infections. The authors present a case of acquired C1-INH deficiency in a patient with Helicobacter pylori infection. Complete eradication of this pathogen was followed by the resolution of symptoms and normalization of serum complement levels. It seems therefore probable that in this patient, acquired C1-INH deficiency was related to Helicobacter pylori infection. To our best knowledge, no similar observations have been published so far. Specific immune reactions are important contributing factors in H. pylori. Excessive consumption of complement by antibodies directed against H. pylori is a potential cause of C1-INH deficiency observed in our case.

Adult↗
PubMed1990

Conservation of the central MHC genome: PFGE mapping and RFLP analysis of complement, HSP70, and TNF genes in the goat.

A degree of conservation of the genes located between class II and class I [central major histocompatibility complex (MHC) genes] is apparent among mammalian species including primates and the mouse. Few others have been analyzed. The caprine MHC is of particular interest, since it has recently been observed that susceptibility to a lentivirus-induced polyarthritis (caprine arthritis) segregates with serologically defined MHC class I antigens. This arthritis resembles, in a number of respects, rheumatoid arthritis in man. Human cDNA probes were used to examine the caprine central MHC and class I and II genes by restriction fragment length polymorphism (RFLP) and by pulsed field gel electrophoresis (PFGE) in order to define the polymorphism and linkage of central MHC genes to class I and class II genes. An outbred population of dairy goats (Saanen, British Alpine, Anglo Nubian, and Toggenberg) was examined for class I and class II RFLPs. Both regions were found to be highly polymorphic. The number of fragments hybridizing to an HLA-B7 probe after Eco RI, Bam HI, Bgl II, or Hind III digestion suggests there may be 10-13 class I genes. The degree of polymorphism was comparable to that reported in the mouse. Limited polymorphism was found in the central MHC genes. The caprine C4 and CYP21 genes were duplicated and demonstrated RFLP with Bam HI, Hind III, Eco RV, and Taq I. An infrequent Taq I C2 polymorphism was found. PFGE revealed substantial conservation of both the order and linkage of the central MHC genes when compared with mouse and man. C4, C2, CYP21, HSP70, and tumor necrosis factor (TNF) genes are all located within 800 kilobase (kb) of the class I loci. Distant from the class I region, the C4, C2, and CYP21 genes are linked on a short genomic segment (180 kb Not I and 190 kb Pvu I fragments). HSP70 cohybridizes with the complement genes on a 380 kb Mlu I fragment. Linkage of HSP70, TNF, and class I genes was found on a single Not I fragment (610 kb). TNF and class I cohybridize on Pvu I (730 kb) and Not I (610 kb) fragments. Conservation of a similar central MHC genomic structure across species argues for functional interaction between the central MHC genes. We postulate selection for these central MHC genes through their role as non antigen-specific regulators of immune response.

Animals↗
PubMedDate not supplied

Complement deficiency: predisposing factor to autoimmune syndromes.

The recognition of the association between complete and partial complement (C) deficiencies and immune complex (IC) mediated diseases, especially SLE, is of clinical and etiopathologic interest. From studies of sera deficient in C1, C4, C2 or C3, the crucial role of these components of the classical pathway in promoting the solubility and clearance of IC has been elucidated. Although complete deficiency of C1, C4 C2 or C3 is rare, partial C4 deficiency also appears to be a common predisposing factor for the development of SLE, with complete C4A deficiency (C4A null) being present in 10 to 15% and heterozygous C4A deficiency present in 50 to 80% of caucasian SLE patients. Most importantly, there is an obvious pathophysiologic relationship between the function of C relative to IC processing and the syndromes which result from C deficiency. Thus, SLE is a prototype for disease characterized by excessive quantities of inappropriately deposited IC. More subtle C component and receptor deficiencies are likely to be predisposing factors for SLE and related autoimmune diseases.

Antigen-Antibody Complex↗
PubMed1985

Activation of the human classical complement pathway by a mouse monoclonal hybrid IgG1-2a monovalent anti-TNP antibody bound to TNP-conjugated cells.

A mouse hybridoma selected and cloned for anti-TNP specificity produced three distinct monoclonal antibody species that were separated on protein A-Sepharose by stepwise acid elution. The IgG1 kappa product of the parental myeloma was eluted at pH 6.0. An IgG2a kappa bivalent anti-TNP antibody was eluted at pH 4.5, whereas elution at pH 5.0 yielded a hybrid IgG1-2a kappa monovalent anti-TNP antibody. The IgG2a molecules agglutinated TNP-conjugated sheep erythrocytes (TNP-ES) and lysed TNP-ES in the presence of normal human serum (NHS). Hybrid IgG1-2a antibody was also capable of lysing the cells in NHS, although it did not agglutinate TNP-ES. A threshold in monovalent antibody input was necessary for the lysis of TNP-ES, indicating a requirement for a minimal density of bound monovalent IgG to trigger complement activation. Lysis occurred in NHS-VBS++ but not in NHS-MgEGTA, and it was associated with a dose-dependent consumption of C1, C4, and C2 hemolytic activities. Quantitation of the antibody bound to TNP-ES when using radiolabeled rabbit anti-mouse Fab antibody demonstrated that for similar inputs, 5.4 times as much bivalent as monovalent antibody bound to TNP-ES. When similar amounts of antibody were effectively bound to TNP-ES, monovalent hybrid IgG1-2a was five times less efficient than bivalent IgG2a to yield 50% cell lysis in the presence of NHS. These results indicate that neither bivalent binding nor the presence of two identical heavy chains are necessary requirements for antibody-dependent activation of the classical complement pathway.

Agglutination↗
PubMed1975

Inhibition by epsilon-aminocaproic acid of the activation of the first component of the complement system.

The influence of EACA on C1 in whole human serum and on C1 and C (see article) as isolated molecules was assessed hemolytically. There was selective inhibition of C1 without effect on the levels of C4, C2, C3, and C9 in whole human serum that was reversed by dialysis. EACA was found to inhibit the intrinsic activation of C1 without inhibiting the already active molecule. This was confirmed by the capacity of trypsin to uncover C1 activity in cellular intermediates formed by C1 treated with EACA that did not evolve in the absence of this extrinsic activating mechanism. Inasmuch as the trypsin-dependent recovery of C1 was incomplete, an effect on binding cannot be excluded.

Aminocaproates↗
PubMed1981

Complement loci of the HLA complex. Studies on families with intra-HLA crossovers and haplotype associations.

We report genetic studies of families with defined crossovers in the HLA complex. Haplotypic associations between the different alleles have been analyzed. The object of the studies has been to determine the precise location of complement loci on the HLA complex on chromosome 6. Based on direct observation of recombinations and on indirect evidence from haplotypes, we postulate that the C4 and Bf loci are located between the HLA-B and -D regions and probably closer to the former. Available information also points towards the same localization for the C2 locus.

Alleles↗
PubMed2001

S-adenosyl-L-methionine is required for DNA cleavage by type III restriction enzymes.

The requirement of S-adenosyl-L-methionine (AdoMet) in the cleavage reaction carried out by type III restriction-modification enzymes has been investigated. We show that DNA restriction by EcoPI restriction enzyme does not take place in the absence of exogenously added AdoMet. Interestingly, the closely related EcoP15I enzyme has endogenously bound AdoMet and therefore does not require the addition of the cofactor for DNA cleavage. By employing a variety of AdoMet analogs, which differ structurally from AdoMet, this study demonstrates that the carboxyl group and any substitution at the epsilon carbon of methionine is absolutely essential for DNA cleavage. Such analogs could bring about the necessary conformational change(s) in the enzyme, which make the enzyme proficient in DNA cleavage. Our studies, which include native polyacrylamide gel electrophoresis, molecular size exclusion chromatography, UV, fluorescence and circular dichroism spectroscopy, clearly demonstrate that the holoenzyme and apoenzyme forms of EcoP15I restriction enzyme have different conformations. Furthermore, the Res and Mod subunits of the EcoP15I restriction enzyme can be separated by gel filtration chromatography in the presence of 2 M NaCl. Reconstitution experiments, which involve mixing of the isolated subunits, result in an apoenzyme form, which is restriction proficient in the presence of AdoMet. However, mixing the Res subunit with Mod subunit deficient in AdoMet binding does not result in a functional restriction enzyme. These observations are consistent with the fact that AdoMet is required for DNA cleavage. In vivo complementation of the defective mod allele with a wild-type mod allele showed that an active restriction enzyme could be formed. Furthermore, we show that while the purified c2-134 mutant restriction enzyme is unable to cleave DNA, the c2-440 mutant enzyme is able to cleave DNA albeit poorly. Taken together, these results suggest that AdoMet binding causes conformational changes in the restriction enzyme and is necessary to bring about DNA cleavage.

Alleles↗
PubMed1981

Complement levels in cigarette smokers: elevation of serum concentrations of C5, C9, and C1-inhibitor.

Serum levels of 13 individual complement component and control proteins were measured in 25 male cigarette smokers and 25 male non-smokers. A significant elevation of the mean serum levels of C5, C9 and C1-inhibitor was demonstrated for the smokers while levels of C1q, C2, C4, C3, C6, C8, Factor B, properdin, C3b inactivator and beta 1H did not differ significantly between the two groups. Serum level of C9 in individual smokers correlated significantly with both the present amount of consumption and cumulative consumption, while C5 level correlated with present consumption. The complement profile in the cigarette smoker is similar to that observed in certain inflammatory conditions. The elevation of C5, C9 and C1-inhibitor levels may reflect the presence of a low grade inflammatory process in the cigarette smoker.

Adolescent↗
PubMed1979

Interaction between components of the human classical complement pathway and immobilized Cibacron Blue F3GA.

The interaction between the complement components in human serum and the dye, Cibacron Blue F3GA, immobilized on cross-linked agarose (Affi-Gel Blue) has been studied. All nine components of the classical complement pathway bound to the dye and could be recovered using a linear salt gradient. With the exception of C5 and C8, all the components were eluted over a narrow NaCl concentration range, with the following yields: C1, 17%; C2, 69%; C3, 92%; C4, 87%; C6, 105%; C7, 109%; C9, 128%. C5 and C8 eluted throughout the NaCl gradient with yields of 103% and 14%, respectively. Since all components could be eluted without substantial contamination by albumin or IgG, this procedure may prove valuable as an initial step in the purification of complement components. In addition, the ability of immobilized Cibacron Blue F3GA to physicallly remove complement components may prove useful for both the decomplementation of serum and in elucidating the role of complement in immunological reactions.

Anthracenes↗
PubMed1977

Interactions between mycoplasma pneumoniae and the first components of complement.

Mycoplasma pneumoniae cells were rounded and killed by fresh guinea pig serum (GPS) which did not contain detectable amounts of antibody. The first component of complement (C1) was bound by M. pneumoniae in considerable amounts from both GPS and purified C1. The C1 bound by the cells was reacting with C4. Sequential addition of C1, C4, C2, and C-ethylenediaminetetraacetate to glass-grown M. pneumoniae cells resulted in rounding of a significant number of cells. M. orale and M. fermentans showed a reduced binding capacity for C1 as compared with M. pneumoniae. Both species were only slowly killed by fresh GPS, whereas M. hominis was as sensitive as M. pneumoniae. The results suggest an antibody-independent interaction between some components of the membrane surface of M. pneumoniae and C1, resulting in an activation of the complement system leading to the killing of the mycoplasma cells.

Animals↗
PubMed1989

Acceleration of site-to-site transfer of C1- by a monoclonal antibody to C1-s.

A monoclonal antibody to human C1-s (a subcomponent of C1-), M365 blocked the complement-mediated lysis of C1(-)-coupled IgM-sensitized sheep erythrocytes (EAIgMC1). However, M365, via its binding to C1-s, did not inhibit C2 activation and only partially inhibited C4 activation, both attributable to the proteolytic action of C1s. Therefore, the inhibition of lysis of EAIgMC1 is not due to the direct effect of antibody binding to C1-s in the C1- molecule. M365, when added to the pre-formed EAIgMC1, deprived the whole C1 molecule from the cells. It was also found that M365-bound C1 could not bind to EAIgM. These phenomena were induced only when M365, one of seven monoclonal antibodies to C1-s, was employed and when IgM antibody-sensitized E was used. The observed C1- liberation and C1 binding inhibition by M365 were found to be less effective when the C4b bearing cells, EAIgMC4, were used. But the addition of M365-bound C1- to EAIgMC4 promoted the formation of the C3 convertase, C4b2a, which caused an incremental lysis of the C4b bearing cells. The results are interpreted to mean that C1-, once complexed with M365, still remains active and acquires the ability to transfer from one C1 binding site on IgM to another to activate the convertases. C4b must be a prerequisite on the cells to induce the effective C1- transfer and resulting increase of C3 convertase sites. We hypothesize that the M365-C1-s association alters the conformation of C1q and thereby leads to the dissociation of whole C1- from IgM. The M365-C1- complex, therefore, can move from site to another.

Animals↗
PubMed2001

Deletion of wboA enhances activation of the lectin pathway of complement in Brucella abortus and Brucella melitensis.

Brucella spp. are gram-negative intracellular pathogens that survive and multiply within phagocytic cells of their hosts. Smooth organisms present O polysaccharides (OPS) on their surface. These OPS help the bacteria avoid the bactericidal action of serum. The wboA gene, coding for the enzyme glycosyltransferase, is essential for the synthesis of O chain in Brucella. In this study, the sensitivity to serum of smooth, virulent Brucella melitensis 16M and B. abortus 2308, rough wboA mutants VTRM1, RA1, and WRR51 derived from these two Brucella species, and the B. abortus vaccine strain RB51 was assayed using normal nonimmune human serum (NHS). The deposition of complement components and mannose-binding lectin (MBL) on the bacterial surface was detected by flow cytometry. Rough B. abortus mutants were more sensitive to the bactericidal action of NHS than were rough B. melitensis mutants. Complement components were deposited on smooth strains at a slower rate compared to rough strains. Deposition of iC3b and C5b-9 and bacterial killing occurred when bacteria were treated with C1q-depleted, but not with C2-depleted serum or NHS in the presence of Mg-EGTA. These results indicate that (i) OPS-deficient strains derived from B. melitensis 16M are more resistant to the bactericidal action of NHS than OPS-deficient strains derived from B. abortus 2308, (ii) both the classical and the MBL-mediated pathways are involved in complement deposition and complement-mediated killing of Brucella, and (iii) the alternative pathway is not activated by smooth or rough brucellae.

Brucella abortus↗