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PubMed1978

Activation of the alternate complement pathway by peptidoglycan from streptococcal cell wall.

Activation of the alternate complement pathway in human serum by several bacterial components was compared. Peptidoglycan from group A streptococcal cell walls was the most active material, on a weight basis, followed by cell walls, protoplast membranes, and whole cells. The group-specific carbohydrate was inactive. Treatment of peptidoglycan with low concentrations of lysozyme or short periods of sonic treatment enhanced complement activation. High concentrations of lysozyme or extended sonic treatment of peptidoglycan destroyed or greatly reduced the capacity to activate complement. Lysozyme treatment of group A streptococcal cell walls or lipopolysaccharide had no measurable effect. Activation of the alternate complement pathway by group D streptococcal cell walls was destroyed by lysozyme. Activity of peptidoglycan was not inhibited by N-acetyl glucosamine, N-acetyl muramic acid, or D-alanine-D-alanine. Conversion of C3 and factored B by peptidoglycan was shown to occur by immunoelectrophoresis and crossed immunoelectrophoresis.

Animals↗
PubMedDate not supplied

Heparin free hemodialysis does not cause fibrin consumptive coagulopathy and maintains alternate pathway complement activation.

Heparin-free hemodialysis allows demonstration of the intradialytic coagulation status not previously possible during standard heparin anticoagulant hemodialysis protocols in patients with end-stage renal disease. No evidence for consumptive coagulopathy was noted in the absence of heparin during hemodialysis with cuprophane hollow fiber dialyzers. Fibrinogen levels, euglobulin lysis time, and platelet counts remained stable throughout 3 hours of heparin-free hemodialysis. Serial thrombin times and platelet aggregation improved during heparin-free hemodialysis. Hemodialyzer volumes and the ultrafiltration coefficient decreased only minimally. The alternate pathway of complement activation associated with hemodialysis blood-membrane interaction is not prevented by heparin-free hemodialysis.

Adult↗
PubMed1979

Chemotaxigenesis and activation of the alternative complement pathway by encapsulated and non-encapsulated Cryptococcus neoformans.

In the presence of serum, whole cells of encapsulated and non-encapsulated Cryptococcus neoformans generated a chemotactic response by neutrophils. Heat inactivation of serum ablated all chemotactic activity. Cryptococcal polysaccharide was not chemotaxigenic. Assays for alternative complement pathway activation such as depletion of alternative complement pathway factor B or electrophoretic conversion of factor B closely paralleled chemotaxis assays. Cells of encapsulated and non-encapsulated C. neoformans activated the alternative complement pathway, whereas cryptococcal polysaccharide was inactive. Failure of the capsular material to activate the alternative pathway was not due to serotype specificity because polysaccharide of several serotypes failed to achieve activation. The results suggest that chemotaxigenesis and alternative complement pathway activation are functions of the yeast cell wall. The results support our proposal that the cryptococcal capsul does not prevent potential opsonins from reaching binding and activation sites at the yeast cell wall or the release of biologically active soluble cleavage products into the surrounding medium; however, cell wall-bound cleavage products remain bound to the cell wall beneath the capsule. Therefore, they are unable to participate as opsonins in phagocytosis.

Animals↗
PubMed1976

Alternative complement pathway: activity levels in allogeneic pregnancy.

Classical and alternative complement pathway activities have been evaluated in sera of women in progressive stages of gestation and in pregnant mice belonging to outbred or inbred matings, as compared to suitable controls. While classical C pathway was found to be unmodified, the alternative one attained in pregnancy significantly higher activity levels. Results are discussed in the light of mother-conceptus relationships.

Animals↗
PubMed1978

Autosomal locus regulates inverse relationship between sialic acid content and capacity of mouse erythrocytes to activate human alternative complement pathway.

The observation that mouse erythrocytes (E(m)) from 21 inbred strains had variable capabilities to activate the human alternative complement pathway permitted the demonstration that membrane sialic acid content was inversely related to activating capacity and was regulated by codominant alleles of a single autosomal locus. Linear regression analysis also demonstrated a significant inverse correlation between the sialic acid content of E(m) from four inbred strains and the concentration of beta1H required for decay-dissociation of the properdin-stabilized amplification convertase on the E(m). E(m) from F(1) hybrids derived from strains with high and low alternative pathway activating capacities and from their backcrosses exhibited the alternative pathway activating capacities expected if the activity were regulated by alleles of a single autosomal locus. That this same locus predominantly regulated the sialic acid content of E(m) was established by the significant inverse correlation between the sialic acid content and the alternative pathway activating capacity of E(m) from mice of the F(1) and backcross generations. Although the fluid phase interaction of C3, B, and [unk]D continuously generates C3b in a reaction augmented by properdin, it is the covalent attachment of C3b to bystander surfaces deficient in sialic acid that activates the alternative complement pathway at that site because of impaired binding of beta1H to C3b on such surfaces. Thus, discrimination between activating and nonactivating surfaces occurs after C3b deposition, and sialic acid deficiency represents the molecular basis for our earlier finding that activating particles circumvent the regulatory actions of the control proteins of the alternative pathway.

Animals↗
PubMed1978

Activation of the alternative complement pathway by human B cell lymphoma lines is associated with Epstein-Barr virus transformation of the cells.

Activation of the alternative complement pathway by human B cell lymphoma lines is correlated with the presence of Epstein Barr virus (EBV) in the cell genome. EBV-negative B cell lymphoma lines produce little activation of the alternative pathway as measured either by C3 deposition on the cell surface or C3 conversion and consumption of alternative pathway activity in the supernatant serum. By contrast, EBV-positive sublines derived by in vitro EBV conversion of EBV-negative parental lines produce considerable activation of the alternative pathway. This membrane-associated complement-activating mechanism reflects an EBV-induced membrane change in these cells and may provide a mechanism whereby EBV-transformed cells are controlled in vivo.

B-Lymphocytes↗
PubMed1978

Activation of the alternative complement pathway by a streptococcal lipoteichoic acid.

A glycerol lipoteichoic acid antigen from Streptococcus pyogenes 1-RP41 was found by rabbit erythrocyte hemolytic assay to activate the alternative complement pathway in human sera. Over a narrow concentration range of the teichoic acid, complement consumption was dose dependent, whereas at higher concentrations of the acid complement consumption could not be detected.

Antigens, Bacterial↗
PubMed1988

Specific antibodies enhance Sephadex-induced activation of the alternative complement pathway in human serum.

Sephadex beads, which resemble cellulose in their basic chemical structure, were used to study the molecular mechanisms by which cellulosic dialysis membranes activate the alternative complement pathway in normal human serum. Sera from different individuals were found to vary in the extent of activation which occurred following incubation with a fixed amount (surface area) of polymer. Preadsorption of serum with an excess of Sephadex at 2 degrees C resulted in loss of activation when the absorbed serum was interacted with fresh Sephadex beads. Acid eluted proteins from absorbed Sephadex restored the capacity of preadsorbed serum to activate complement in the presence of fresh Sephadex. Adsorption of the immunoglobulin G (IgG) fraction and of F(ab')2 fragments from IgG prepared from the plasma of a normal individual with Sephadex, resulted in the specific binding of some IgG and F(ab'2) molecules to the particles. IgG and F(ab')2 coated beads activated complement in Sephadex-adsorbed serum. Thus, specific anti-dextran IgG antibodies trigger activation of the alternative complement pathway by Sephadex in human serum. The effect is independent of the Fc region of IgG. These results suggest that specific antibodies could be important in determining complement activation in vivo in patients undergoing haemodialysis with cellulosic membranes.

Adsorption↗
PubMed1986

Alternative complement pathway activation by C4b deposited during classical pathway activation.

Sheep erythrocytes (E) sensitized with anti-E antibody (A) were reacted with guinea pig C1 (C1gp) and human C4 (C4hu) or guinea pig C4 (C4gp) to prepare EAC1, 4b. Treatment of the EAC1, 4b with a buffer containing EDTA removes C1rgp and C1sgp, resulting in the formation of EAC4b. EAC4b prepared in this way were found to be lysed by human or guinea pig serum in a gelatin Veronal-buffered saline containing 2 mM MgCl2 and 8 mM EGTA (Mg-EGTA-GVB). In the hemolytic sensitivity of EAC4bhu, essentially no difference was noted whether IgG or IgM antibodies were used for preparation of EAC4bhu. The extent of the hemolysis of EAC4bhu was dependent on the dose of C4bhu. Because EAC4bhu were lysed even by C2-deficient human serum, C3 convertase of the classical complement pathway would not be involved in the hemolysis of EAC4bhu. Furthermore, the reactivity of EAC4bhu with serum in Mg-EGTA-GVB remained even after treatment of the intermediate cells with 1 mM PMSF, indicating that any remaining C1gp was not responsible for the hemolysis. Therefore, the hemolysis of EAC4b by sera in Mg-EGTA-GVB was considered to be mediated via activation of the alternative complement pathway (ACP). Pretreatment of EAC4bhu with anti-C4hu antibody or C4-binding protein suppressed the hemolysis of EAC4bhu via the ACP activation. Furthermore, EAC4bhu were more sensitive to hemolysis by the reaction with a mixture of C3, B, D, and H followed by rat serum in EDTA-GVB than EAC1qgp were. These results indicate that C4b molecules on the cell membrane participate in the activation of ACP.

Animals↗
PubMed1979

Staphylococcus aureus opsonization mediated via the classical and alternative complement pathways. A kinetic study using MgEGTA chelated serum and human sera deficient in IgG and complement factors C1s and C2.

Staphylococcus aureus opsonization was studied kinetically by: (1) determination of the uptake of [3H]-thymidine labelled bacteria by human PMN's; (2) fluorescent anti-C3 and anti-IgG staining of opsonized bacteria; and (3) measuring bacterial complement consumption. Maximum opsonization in normal serum occurred within 5 min of incubation. About 80% of staphylococci were then taken up by PMN's, and IgG and C3b could be detected on the bacterial surface. In the absence of a functional classical complement pathway, as in sera deficient in C1s and C2 and in MgEGTA chelated serum, maximal opsonization was only achieved after 30--60 min incubation. Opsonization in IgG deficient serum occurred at a rate similar to that found in C2 deficient or MgEGTA chelated serum. Opsonization was greatly enhanced when sera were reconstituted. It was concluded that in IgG deficient serum Staphylococcus aureus opsonization is mediated via the alternative complement pathway. Dilution of normal serum primarily affected the classical complement pathway, resulting in a decreased rate of opsonization. In normal serum IgG did not appear to be a rate-limiting factor. S. Aureus opsonization was best studied by the phagocytosis assay and the fluorescent-antibody technique. Measuring haemolytic complement consumption was found to be an insensitive indicator of bacterial complement activation and opsonization.

Complement Activation↗
PubMed1989

Phagocytosis of particulate activators of the human alternative complement pathway through monocyte beta-glucan receptors.

Human monocytes phagocytose particulate activators of the alternative complement pathway through beta-glucan receptors in the absence of opsonins. Recognition of soluble beta-glucans by monocytes selectively inhibits ingestion of particulate activators and has no effect on responses mediated by monocyte receptors for Fc-IgG, complement, or fibronectin. The smallest ligand unit recognized by monocyte beta-glucan receptors is an acid-resistant heptaglucoside present in yeast cell walls. Mouse monoclonal anti-beta-glucan antibodies have been prepared, one of which completely neutralizes the inhibitory capacity of the HPLC-purified heptaglucoside. This antibody has been used as immunogen for the preparation of an anti-Id. The pretreatment of monocytes with low concentrations of anti-Id inhibits monocyte ingestion of zymosan particles but not EsIgG, suggesting that this antibody has specificity for monocyte beta-glucan receptors and is a powerful probe for further receptor studies. Other receptors with specificities for carbohydrates are also present on mononuclear phagocytes. Receptors for mannose/fucose and those for galactose have been isolated and cloned. The development of probes, such as structural analogs of the active heptaglucoside and the anti-Id, will bring the beta-glucan receptors to a similar stage of definition. A major factor that adds a considerable degree of difficulty to studies of the beta-glucan receptors and is not shared by the other receptors for carbohydrates is the requirement for structural conformations provided by the alignment of several glucose units rather than the recognition of a hexose residue in, for example, a glycoconjugate. The designation of these receptors as beta-glucan receptors has inadvertently taken us into a new area of nonimmune defense. Animal studies indicate that beta-glucans with 1,3- and/or 1,6-linkages are active pharmacologic agents that rapidly confer protection to a normal host against a variety of biologic insults. The beta-glucan receptors provide a mechanism by which a heightened state of host responsiveness is initiated.

Animals↗
PubMed1988

Activation of the alternative complement pathway and generation of stimulating factors for granulocytes by glass fibers.

Continuous-filament glass fibers coated with organic agents, candidate asbestos substitutes, were assessed for their ability to elicit from normal human serum complement-derived cleavage products which are able to stimulate the chemotaxis and the respiratory burst of polymorphonuclear leukocytes. Glass fibers generated chemoattracting and respiratory stimulating factors for polymorphonuclears from human serum. The effect was dose related for chemotaxis from the serum fiber concentration of 75 micrograms/ml to 1,250 micrograms/ml. The serum chemoattracting activity, as well the respiratory stimulation, were dramatically impaired when serum had been preliminarily absorbed with antiC5 antiserum. Since the impairment of chemotactic activity occurred also in the presence of EDTA, but not in the presence of EGTA, we assumed an activation of the alternative complement pathway. Glass fibers were studied in comparison to a UICC sample of Canadian chrysotile asbestos, which is able to activate in vitro the alternative complement pathway. Glass fibers exhibited less ability than asbestos fibers to generate complement cleavage products with chemotactic activity for polymorphonuclears; however, they produced an activity about equal to 80% of a chemotactic standard stimulus such as zymosan-activated plasma.

Asbestos↗
PubMed1978

Activation of the alternate complement pathway in Staph. aureus infective endocarditis and its relationship to thrombocytopenia, coagulation abnormalities, and acute glomerulonephritis.

Twenty-four patients with infective endocarditis (IE) are described, fourteen with Staph. aureus and ten with other organisms. Despite the acute nature of the infection, ten of the fourteen with Staph. aureus IE were hypocomplementaemic; six of these ten had normal levels of C4 associated with low C3 levels, suggesting activation of the alternate complement pathway. Factor B (C3PA) was also low in three of these six cases. In the ten patients with non-Staph. IE, three had hypocomplementaemia with low levels of C4, C3, and Factor B, probably due to C1 (classical pathway) activation with feedback activation of the alternate pathway. In addition, thrombocytopenia was noted in nine of the twenty-four patients and was associated with hypocomplementaemia; the degree of renal insufficiency noted in these patients also correlated with hypocomplementaemia. In Staph. aureus IE thrombocytopenia and hypocomplementaemia, occurring early in the course of the disease, may be due to a non-immune interaction of Staph. cell wall products (Protein A) with immunoglobulin, complement components, and thrombocytes.

Acute Disease↗
PubMed1989

Two forms of guinea pig factor B of the alternative complement pathway with different molecular weights.

Two forms of guinea pig factor B (B) of the alternative complement pathway with different mol. wts (Mr) have been isolated from plasma and characterized. The Mr of the two B species, tentatively termed B1 and B2, were estimated to be about 100,000 and 96,000, respectively, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Incubation of B with guinea pig C3 and human factor D (D) in the presence of Mg2+ generated two cleavage fragments of B, namely Ba and Bb. Although the Bb fragments showed the same migration corresponding to an Mr of 62,000, Ba fragments showed different mobilities corresponding to an Mr of 38,000 from B1 and 34,000 from B2. Digestion of B1-Ba, the Ba fragment derived from B1, and B2-Ba, the Ba fragment derived from B2, with endoglycosidase F resulted in a band at Mr 30,000 on an SDS-PAGE in both cases, indicating a difference in structure of the asparagine-linked oligosaccharide moiety in B1-Ba and B2-Ba. No difference in antigenicity was noted between B1 and B2 on immunodiffusion with anti-B sera. Immunoblotting analysis showed that all individual Hartley guinea pigs examined in this study possessed both B1 and B2 at similar levels, as determined by the intensity of staining of their sera. Furthermore, treatment of their serum with zymosan led to the generation of two Ba species corresponding to the Ba fragments from B1 and B2. The capacity to form C3/C5 convertase, as determined by hemolytic assay, was found to be similar between B1 and B2. Furthermore, kinetics of the decay of C3 convertase showed the same half-life of 3.0 min at 30 degrees C. The NH2-terminal amino acid sequences of B1 and B2 and their Bb fragments were determined and found to be identical.

Amino Acid Sequence↗
PubMed1990

Curdlan, a (1----3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO13140, activates the alternative complement pathway by heat treatment.

From the results of consumption experiments of guinea pig complement, Curdlan, a (1----3)-beta-D-glucan obtained from Alcaligenes faecalis var. myxogenes IFO13140, has been found to lack the ability to activate complement when unheated or preheated at either 40 degrees C or 50 degrees C. However, Curdlan heated at or above 60 degrees C increased complement consumption. This activation, dependent on the temperature of the Curdlan, was via the alternative complement pathway as assessed by cleavage of factor B into Ba and Bb fragments. These results suggest a substantial change must occur in Curdlan with heat treatment for alternative pathway activation.

Alcaligenes↗
PubMed1991

Reconstitution of C5 convertase of the alternative complement pathway with isolated C3b dimer and factors B and D.

C5 convertase of the alternative complement pathway is a trimolecular complex consisting of two molecules of C3b and one molecule of Bb. We previously proposed a model of the alternative pathway C5 convertase in which the second C3b molecule binds covalently to the first C3b molecule bearing Bb, and the C5 molecule binds to each C3b molecule of the covalently linked C3b dimer, resulting in its appropriate presentation to the catalytic site on Bb. In the present study, we purified the covalently linked C3b dimer and reconstituted the C5 convertase with the C3b dimer and factors B and D to obtain evidence in support of this model. An insoluble glucan, OMZ-176, was incubated with human serum to activate the alternative pathway and to allow formation of the alternative C5 convertase on the surface of the glucan, and the glucan bearing the C5 convertase was then solubilized by incubation with glucosidases. In this way, the covalently linked C3b dimer was obtained in solution without using a detergent. The C3b dimer was then separated from enzymes, C3b monomer, C3b oligomer, and other materials by chromatographies. SDS-PAGE analysis demonstrated that the purified C3b dimer had intact alpha'-chains. Alternative pathway C5 convertase was reconstituted when the isolated C3b dimer was incubated with factors B and D. The presence of P enhanced C5 convertase formation threefold. These results support the notions that the formation of the covalently linked C3b dimer is a general phenomenon associated with activation of the alternative pathway and that the C3b dimer acts as a part of the C5 convertase.

Complement C3-C5 Convertases↗
PubMed1990

Membrane damage to Escherichia coli and bactericidal kinetics by the alternative complement pathway of channel catfish.

1. Increased permeability of cytoplasmic membranes in Escherichia coli was a consequence of alternative complement pathway (ACP) activity of serum of channel catfish, Ictalurus punctatus. Evidence was provided by beta-galactosidase activity extracellularly when E. coli was incubated with catfish serum. 2. Lesions were detected on outer membranes of E. coli following exposure to catfish serum. 3. Catfish ACP induced a temporal sequence of pre-killing and killing phases. 4. Loss of cell viability, killing rate and cytoplasmic enzyme release increased with increasing serum concentrations. 5. By incubating E. coli with sera treated to remove complement, both release of cytoplasmic enzyme and bactericidal activity were eliminated. 6. Lethal activity associated with channel catfish ACP against Gram-negative bacteria was functionally comparable to that seen in mammalian and reptilian systems.

Animals↗
PubMedDate not supplied

Participation of immunoglobulin and the alternative complement pathway in opsonization of Bacteroides fragilis and Bacteroides thetaiotaomicron.

Studies were conducted to determine the requirements for immunoglobulin and complement in opsonization of Bacteroides fragilis and Bacteroides thetaiotaomicron. The ability of human sera depleted of immunoglobulin or of components of complement to promote the phagocytosis and intracellular killing of the two strains of Bacteroides by human leukocytes was measured in vitro under anaerobic conditions. Neither hypogammaglobulinemic sera nor pooled normal human serum that was heated at 56 C for 30 min supported phagocytosis and killing of the two strains of Bacteroides. Neither sera depleted of terminal complement components by treatment with inulin or cobra venom factor nor human serum deficient in C8 supported phagocytosis of the tested strains. In addition, pooled normal human serum depleted of C3, factor B, or factor D did not support phagocytosis of either strain. Dose-dependent restoration of the opsonic activity of factor B-depleted serum was accomplished by purified human factor B but not by human C2. The results indicate that immunoglobulin and components of the alternative comed in this study.

Animals↗