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Results for “Complement Inactivator Proteins”

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At least 631 records · Page 35Linked to original sources
PubMed1984

C3 nephritic factor in a patient with recurrent Neisseria meningitidis infections.

A 15-year-old female experienced two systemic infections with N.meningitidis (group C and B) within a two months period. Classical as well as alternative pathway CH50 determinations on the patients serum showed no lysis. All individual complement factor concentrations, except for C3, were found to be within the reference area. Crossed immunoelectrophoretic analysis of C3 revealed no demonstrable native C3. The patient had normal levels of C3c and a markedly elevated C3d concentration. Serum from the patient was found to convert all native C3 in normal sera within 10 minutes at 37 degrees C. The active converting principle, present in the IgG fraction activated C3 in C4-depleted serum, and had a dose dependent stabilizing effect on the EA-C3bBb complex. The isolated factor showing the characteristics of C3 nephritic factor (C3 NeF), was unchanged in the patients serum over a ten months observation period. Circulating immune complexes (IC) could not be demonstrated by a C1q-dependent assay but the patients capacity to solubilize preformed IC in vitro was virtually abolished. The patient had no signs of renal disease or lipodystrophy.

Adolescent↗
PubMed1994

Anti-complement activity of oleanolic acid: an inhibitor of C3-convertase of the classical complement pathway.

Oleanolic acid is a naturally occurring compound, isolated from Luffa cylindrica, which inhibits the in-vitro immunohaemolysis of antibody-coated sheep erythrocytes by guinea-pig serum. In further experiments this reduced immunohaemolysis was found to be due to inhibition of the C3-convertase of the classical complement pathway. The threshold concentration for inhibition of C3-convertase was 100 micrograms mL-1. However, higher concentrations of oleanolic acid showed constant inhibitory effects on immunohaemolysis. Oleanolic acid also exhibited weak inhibitory effects on individual components of the complement system.

Animals↗
PubMed2006

Identification of the gene encoding the FhbB protein of Treponema denticola, a highly unique factor H-like protein 1 binding protein.

The gene encoding the Treponema denticola factor H-like protein 1 (FHL-1) binding protein, FhbB, was recovered and characterized. Sequence conservation, expression, and properties of FhbB were analyzed. The identification of FhbB represents an important step in understanding the contribution of FHL-1 binding in T. denticola pathogenesis and in development of periodontal disease.

Bacterial Proteins↗
PubMed1971

Specific inactivation of the fourth complement component. I. In vivo studies.

Intravascular injection of guinea pigs with the fourth complement component (C4) inactivator from shark serum resulted in severe serum C4 depletion that lasted for several hours. Active and direct passive Arthus reactions did not develop or were extremely mild in such C4 inactivator-treated animals as judged by gross and histological observation. In consideration of the specificity of the C4 inactivator, its independence of cofactors, and its failure to generate biologically active materials in the process of C4 inactivation, it is concluded that complement-dependent immune injury can be suppressed or avoided by interruption of the complement cascade at a single early step. The depression of the Arthus reaction beyond the time of C4 recovery prompted quantitative speculations concerning (i) the in vivo rate of C5a generation under conditions of limited C4 supply and (ii) the "saturation" of immune complexes. This view is supported by in vitro demonstration of functional inactivation or "saturation" of immune precipitates by repeated incubation with fresh guinea pig complement. It seems therefore conceivable that even temporary complement inactivation may have a profound beneficial effect on complement-dependent immune injuries.

Animals↗
PubMed1971

Specific inactivation of the fourth complement component. II. In vitro studies.

The fourth complement component (C4) inactivator obtained from nurse shark serum was used to inactivate C4 in fresh sera of various mammalian species. These hemolytically inactive sera, which contained the remaining eight complement components in unaltered form, were used (i) as a source of the first complement component (C1) for the generation of sensitized sheep erythrocytes (EA)-C1 and (ii) as a homologous reagent for the measurement of C4 activity with EA-C1 or EA in fresh, normal serum of guinea pigs, humans, dogs, and pigs.

Animals↗
PubMed1985

Isolation and partial characterization of staphylococcal decomplementation antigen.

A substance with potent decomplementation activity was isolated from staphylococcal culture supernatants by polyethylene glycol precipitation, DEAE-ion-exchange and Sephacryl chromatography, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified substance exhibited all the characteristics of the decomplementation antigen (DA) previously detected in unfractionated culture supernatants. It contained glucosamine and phosphorus and was provisionally identified as extracellular, water-soluble teichoic acid of Staphylococcus aureus. DA was entirely resistant towards the action of proteases, DNase, RNase, or lysostaphin and withstood boiling for 30 min. Its electrophoretic mobility in agarose gels at pH 8.7 was approximately double that of human serum albumin. The molecule eluted in a molecular-weight region of 70,000 to 120,000 on Sephacryl S-300 and sedimented as a symmetrical 3 to 4 S moiety in sucrose density gradients. It migrated near the dye front on 12.5% sodium dodecyl sulfate-polyacrylamide gels and remained undenatured after boiling in sodium dodecyl sulfate. DA formed a symmetrical immunoprecipitate upon crossed immunoelectrophoresis against pooled human immunoglobulin G. It was identified as the major extracellular antigen present in unfractionated S. aureus culture supernatants that is precipitable by naturally occurring human immunoglobulin G antibodies. Immune complexes forming between DA and human immunoglobulin G exhibited an extraordinary capacity to activate the classical complement pathway. Micro- or nanogram amounts of purified antigen added to antibody-containing human serum effected rapid and complete consumption of C3, C4, and C5. The biochemical and biological properties of DA single out this molecule for an important role in suppressing the opsonizing activity of host complement through induction of abortive complement consumption in the fluid phase.

Antigens, Bacterial↗
PubMed1972

Fatal anaphylaxis-like reaction induced by yeast mannans in nonsensitized mice.

Some yeast mannans increased vascular permeability and caused anaphylaxis-like reactions, fatal in some cases, in nonsensitized CFW mice. In SWR mice deficient in the complement system component C5, anaphylactic shock did not develop after the injection of mannans but was readily induced by goat serum after the mice had been sensitized with Bordetella pertussis and goat serum. The observed biological activity of the yeast mannans appears to depend upon the alpha(1 --> 2) and alpha(1 --> 6) linkages in their main chain. Their relative inactivity in C5-deficient mice and the consumption of whole hemolytic complement after their addition to normal mouse serum suggest that yeast mannans may activate late-acting complement components to produce anaphylatoxin from complement components C5 and C3.

Anaphylaxis↗
PubMed1972

Enhancement of hemagglutination inhibition by complement.

Experiments were conducted to determine the effect of specific antibody and complement on hemagglutination inhibition of influenza virus. It was found that early immunoglobulin M antibody to influenza virus inhibited the hemagglutinating capacity of the virus. When fresh guinea pig serum was added, the inhibiting capacity of the serum was elevated from four- to eightfold When guinea pig serum was treated with known complement inhibitors, it lost its capacity to enhance hemagglutination. The use of functionally purified complement components indicated that the first, second, and fourth components were necessary and sufficient for enhancement of hemagglutination inhibition by specific antibody to influenza virus.

Animals↗
PubMed2006

Expression microarray and mouse virulence analysis of four conserved two-component gene regulatory systems in group a streptococcus.

Group A streptococcus (GAS) is a gram-positive human bacterial pathogen that causes diseases ranging from relatively mild epithelial cell surface infections to life-threatening invasive episodes. Much is known about the extracellular molecules that contribute to host-pathogen interactions, but in contrast, far less information is available about regulatory genes that control the expression of individual or multiple GAS virulence factors. The eight GAS genomes that have been sequenced have 12 conserved two-component gene regulatory systems (TCSs), but only 3 of these 12 have been studied in detail. Using an allelic replacement strategy with a nonpolar cassette, we inactivated the response regulator of four TCSs that have only weak homology with TCS genes of known or inferred function in other bacteria. The mutant strains were analyzed by expression microarray analysis at four time points and tested in two mouse infection models. Each TCS influenced expression (directly or indirectly) of 12 to 41% of all chromosomal genes, as assessed by growth in Todd-Hewitt broth and a custom Affymetrix GeneChip. None of the isogenic mutant strains was significantly altered for mouse virulence based on intraperitoneal inoculation. Similarly, compared to the wild-type strain, there was no significant difference in skin lesion size for three of the four mutants. In contrast, the DeltaM5005_Spy_0680 mutant strain produced significantly larger abscesses after subcutaneous inoculation into mice, consistent with a hypervirulence phenotype. The mutant strain had significantly higher in vitro expression of several proven and putative virulence genes, including scpA, encoding a peptidase that inactivates complement protein C5a. Together, the data provide new information about previously uncharacterized GAS TCSs.

Animals↗
PubMed2006

Molecular analyses of the interaction of Borrelia hermsii FhbA with the complement regulatory proteins factor H and factor H-like protein 1.

Borrelia hermsii, the primary etiological agent of tick-borne relapsing fever in North America, binds the complement regulatory protein factor H (FH) as a means of evading opsonophagocytosis and the alternative complement pathway. The ability of FH-binding protein A (FhbA) to bind FH-like protein 1 (FHL-1) has not been assessed previously. In this study, using a whole-cell absorption assay, we demonstrated that B. hermsii absorbs both FH and FHL-1 from human serum. Consistent with this, affinity ligand binding immunoblot analyses revealed that FH constructs spanning short consensus repeats 1 to 7 and 16 to 20 bind to FhbA. To investigate the molecular basis of the interaction of FhbA with FH/FHL-1, recombinant FhbA truncated proteins were generated and tested for FH/FHL-1 binding. Binding required determinants located in both the N- and C-terminal domains of FhbA, suggesting that long-range intramolecular interactions are involved in the formation and presentation of the FH/FHL-1-binding pocket. To identify specific FhbA residues involved in binding, random mutagenesis was performed. These analyses identified a loop region of FhbA that may serve as a contact point for FH/FHL-1. The data presented here expand our understanding of the pathogenic mechanisms of the relapsing fever spirochetes and of the molecular nature of the interaction between FH/FHL-1 and FhbA.

Amino Acid Sequence↗
PubMed2006

Evidence that the BBA68 protein (BbCRASP-1) of the Lyme disease spirochetes does not contribute to factor H-mediated immune evasion in humans and other animals.

BBA68 (BbCRASP-1) of the Lyme disease spirochetes binds human factor H (FH) and FH-like protein 1 (FHL-1). Here we assess transcription of the BBA68 gene and production of BBA68 in infected mice and humans using real-time reverse transcriptase PCR and immunoblotting. The species specificity of FH binding to BBA68 was also tested. The data suggest that BBA68 does not play an important role in immune evasion in animals.

Amino Acid Sequence↗
PubMed2000

Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant.

Intravascular routes of administration can provide a means to target gene- and virus-based therapies to multiple tumor foci located within an organ, such as the brain. However, we demonstrate here that rodent plasma inhibits cell transduction by replication-conditional (oncolytic) herpes simplex viruses (HSV), replication-defective HSV, and adenovirus vectors. In vitro depletion of complement with mild heat treatment or in vivo depletion by treatment of athymic rats with cobra venom factor (CVF) partially reverses this effect. Without CVF, inhibition of cell infection by HSV is observed at plasma dilution as high as 1:32, while plasma from CVF-treated animals displays anti-HSV activity at lower dilutions (1:8). When applied to the therapy of intracerebral brain tumors, in vivo complement depletion facilitates the initial infection (assayed at the 2-day time point) by an intra-arterial replication-conditional HSV of tumor cells, located within three separate and distinct human glioma masses. However, at the 4-day time point, no propagation of HSV from initially infected tumor cells could be observed. Previously, we have shown that the immunosuppressive agent, cyclophosphamide (CPA), facilitates the in vivo propagation of an oncolytic HSV, delivered intravascularly, within infected multiple intracerebral masses, by inhibition of both innate and elicited anti-HSV neutralizing antibody response (K. Ikeda et al., Nat. Med. 5:881-889, 1999). In this study, we thus show that the addition of CPA to the CVF treatment results in a significant increase in viral propagation within infected tumors, measured at the 4-day time period. The concerted action of CVF and CPA significantly increases the life span of athymic rodents harboring three separate and large glioma xenografts after treatment with intravascular, oncolytic HSV. Southern analysis of viral genomes analyzed by PCR reveals the presence of the oncolytic virus in the brains, livers, spleens, kidneys, and intestine of treated animals, although none of these tissues displays evidence of HSV-mediated gene expression. In light of clinical trials of oncolytic HSV for malignant brain tumors, these findings suggest that antitumor efficacy may be limited by the host innate and elicited humoral responses.

Adenoviridae↗