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At least 109 records · Page 6Linked to original sources
PubMed1989

Biocompatibility of urinary catheters. Effect on complement activation.

The ability of 2 brands of urinary catheters to activate the complement system in vitro as a marker of biocompatibility was investigated. Pieces of a silicone/latex catheter and an all-silicone catheter were incubated in human serum. Complement activation was tested in 2 enzyme immunoassays, one evaluating C3 activation and the other the terminal complement complex (TCC) formation. The silicone/latex catheter caused considerably more complement activation in both assays than did the all-silicone one. The findings are in agreement with previous results of tissue toxicity tests. The methods presented may prove valuable for the practical purpose of testing the biocompatibility of urinary catheters.

Biocompatible Materials↗
PubMed1988

Complement activation is not required for IgG-mediated suppression of the antibody response.

Feedback suppression of the antibody response by IgG is known to be dependent on intact Fc regions. However, it is not clear which of the Fc-mediated effector functions is required. In the present report we have studied whether ability or inability of the IgG antibodies to activate the complement system was of consequence for their immunosuppressive effect. First, a monoclonal IgG1-anti-2,4,6-trinitrophenyl (TNP) antibody, unable to activate complement via the classical or alternate pathway, was shown to be able to inhibit more than 90% of the in vivo sheep erythrocyte-specific antibody response in mice when TNP coupled to sheep erythrocytes was used as antigen. Second, we investigated the immunosuppressive ability of a non-complement-activating mutant IgG2a-anti-TNP monoclonal antibody. The mutant differs from the wild type by a single amino acid substitution in the CH2 domain leading to inability to fix complement factor C1q. However, the mutant has the same affinity for antigen and the same Fc receptor-binding capacity as the wild type antibody. It is demonstrated that the mutant was as efficient as the wild type antibody in inhibiting an in vitro antibody response to TNP-coupled sheep erythrocytes. These findings confirm the non-determinant specificity and Fc dependence of IgG-mediated suppression, and show that the Fc-mediated effector mechanism is independent of complement activation. The results instead suggest binding to Fc receptors as a necessary step in feedback immunosuppression and favor inactivation of B cells by cross-linking of Fc and antigen receptors on their surface rather than elimination of antigen by complement-dependent phagocytosis as the effector mechanism.

Animals↗
PubMed1981

Complement activation and neutropenia occurring during cardiopulmonary bypass.

Complement activation and pulmonary leukostasis with neutropenia occur in hemodialysis and filtration leukapheresis, with attendant pulmonary dysfunction. Wondering whether similar phenomena might attend cardiopulmonary bypass (CPB), we studied 34 patients undergoing coronary artery bypass operations. As in the other extracorporeal circulation systems, neutropenia (mean 44.7% +/- 4.3% SEM of prebypass PMN count) occurred during the first half hour of bypass and then a rebound neutrophilia followed. CH50 and C3H50 fell 22% to 25% (p for CH50 less than 0.01) during bypass, but C3 conversion and C5a were not demonstrable in patient plasmas. Nonetheless, polymorphonuclear neutrophils (PMNs) harvested late in bypass showed low adherence to nylon and selective chemotactic and aggregative insensitivity to C5a--functional aberrations which are seen after exposure to activated complement. Furthermore, smaller infusions of activated complement into animals produced neutropenia than were required to achieve a detectable [C5a] in the plasma. We conclude that neutropenia during CPB probably results from complement activation below the threshold of detection; complement-stimulated PMNs deserve study as possible mediators of tissue injury occurring during CPB.

Agranulocytosis↗
PubMed1992

Differences of two Borrelia burgdorferi strains in complement activation and serum resistance.

Complement activation and serum resistance of the Borrelia burgdorferi strains B31 (American strain) and PKo (European strain) were compared. In 25% (v/v) normal human serum (NHS) free of B. burgdorferi-specific antibodies the cells of the PKo strain were high activators of complement as indicated by rapid and strong C9 consumption, by deposition of up to 336763 C9 molecules per cell and by the formation of the terminal complement complex on the cell surface. By comparison, complement activation by the B31 strain was low with 5.4-fold less C9 deposited per cell. The addition of B. burgdorferi-specific antibodies to NHS either as purified IgG or heat-inactivated patient sera, had no influence on the results with both strains. After an incubation period of 2h at 37 degrees C in 25% (v/v) NHS most cells of the PKo strain had lost their viability as indicated by cell immobilization and failure to multiply in subcultures. In addition, extensive cell fragmentation and bleb formation were observed in the electron microscope. In contrast, the B31 strain remained alive and morphologically intact after the same incubation with NHS. We conclude from our results that complement activation and serum resistance are properties which differ considerably between isolated strains of B. burgdorferi.

Antibodies, Bacterial↗
PubMed1989

Different oxygenators for cardiopulmonary bypass lead to varying degrees of human complement activation in vitro.

Complement activation was studied in vitro with six different membrane and bubble oxygenators for cardiopulmonary bypass. There was a similar increase in terminal (C5 to C9) activation with all oxygenators (p less than 0.001), ranging from 281% (117% to 444%) to 453% (225% to 680%) after 60 minutes (median and 95% confidence intervals). C3 activation was not observed with a hollow fiber membrane and a soft shell bubble oxygenator. On the other hand, a capillary membrane, a sheet membrane, a nonporous membrane, and a hard shell bubble oxygenator all induced a similar increase in C3 activation (p less than 0.01), ranging from 107% (23% to 346%) to 272% (88% to 395%) after 60 minutes. The differences in C3 activation could not be explained by the blood contact materials or any other single factor known to induce activation, which suggests that overall complement activation during cardiopulmonary bypass is a multifactorial effect. The tubing set per se induced only minor C3 activation but contributed to the overall formation of terminal complement complex. The study further indicates that an arterial line blood filter prevents activated neutrophils from being reinfused to the patient and should be used regardless of type of oxygenator.

Cardiopulmonary Bypass↗
PubMed1983

Complement activation in shock associated with a surgically provoked bacteriaemia.

The activation of complement (C) factors in a patient exhibiting an anaphylactoid shock 10 min after the initiation of transurethral coagulation of vesical papillomas was studied. Streptococcus faecalis was cultured from he urine before and after the shock and from the blood on two occasions within 2 days after the shock. The shock was associated with a marked but transient complement activation as judged from serial determinations of C3d and C3c by doubledecker rocket immuno electrophoresis and native C3 and C3c by crossed immuno electrophoresis. Conventional total C3 quantitation by rocket immuno electrophoresis did not reveal the activation. A decrease of native C4 to 20% of normal values and the appearance of C4 split products indicated classical pathway activation. Factor B conversion showed the alternative pathway to be involved as well. Total haemolytic complement activity was temporarily reduced, increasing without reaching normal values within 20 hours. The results indicated that the classical pathway was transiently activated, pointing to an acute antigen-antibody reaction, probably caused by the entrance of bacteria and bacterial products into the circulation of an immunized host.

Anaphylaxis↗
PubMed1991

Neutrophil polarization and immunoelectrophoresis assays in the study of complement activation by biomaterials.

The neutrophil polarization assay, a technique used to measure chemotaxis, was adapted to examine complement activation. Complement activation in serum which had been incubated with metallic and polymeric biomaterials was examined using the neutrophil polarization assay and immunoelectrophoresis assay. In agreement with previous publications, nylon activated the complement cascade, but PTFE did not. The neutrophil polarization assay was found to be the most sensitive technique for examining complement activation by endotoxin but the immunoelectrophoresis assay is the technique most sensitive for detecting complement activation by cobalt powder. In both assays, complement activation was not detected in serum incubated with chromium powder. However, serum incubated with silver and nickel powder stimulated neutrophils to polarize indicating that these powders may activate complement.

Biocompatible Materials↗
PubMed1994

Effects of complement activation products on the synthesis of decay accelerating factor and membrane cofactor protein by human mesangial cells.

We previously demonstrated that activation of terminal complement components (C8 and/or C9) increases the synthesis and expression of decay accelerating factor (DAF) on human glomerular cells. DAF is a cell membrane-associated complement regulatory protein that inhibits complement activation on cell surfaces. In the present studies we evaluated, first, the mechanisms by which complement activation stimulates DAF synthesis, and second the effect of complement activation on the synthesis. and expression of membrane cofactor protein (MCP), another complement regulatory protein, by human mesangial cells (HMC) in culture. Complement activation by immune complexes resulted in increased DAF mRNA levels by at least two mechanisms: deposition of activated C3 on HMC and generation of soluble complement activation products, specifically C5a. The increase in DAF mRNA levels induced by activated C3 or C5a was short lived (less than 4 hr). In contrast, the up-regulation of DAF mRNA levels induced by activation of the complete complement cascade persisted for at least eight hours. The effect of complement activation on DAF mRNA levels was not affected by cycloheximide, a protein synthesis inhibitor. However, cycloheximide alone resulted in a significant up-regulation of DAF mRNA levels on HMC. In contrast to those findings complement activation did not cause an up-regulation of MCP mRNA, nor an increase in the synthesis of this protein. However, by FACS, complement produced a small but significant increase of MCP protein levels on HMC. In conclusion, both MCP and DAF are present on HMC. Several activated complement components are capable of increasing DAF mRNA levels, but DAF protein levels increase only after activation of the whole complement cascade.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1988

Lack of complement activation by human IgA immune complexes.

Complement activation may play an important role in renal injury associated with glomerular deposition of IgA immune complexes. The ability of naturally occurring human IgA immune complexes (IgA-IC) and covalently cross-linked human IgA oligomers (X-IgA) to activate complement were examined in vitro and in vivo. Large-sized IgA-IC were isolated from a patient's serum by affinity purification (Jacalin-Sepharose) and gel chromatography. Stable X-IgA were prepared by chemical cross-linking with a heterobifunctional reagent, N-succinimdyl 3-(2-pyridyl-dithio) propionate (SPDP). Treatment of fresh normal human serum with large amounts of either IgA-IC or X-IgA failed to activate C3. The C3 consumption was measured immunochemically by the decrease of the B antigen on the native C3 and by the generation of iC3b. Addition of these complexes to serum did not result in cleavage of factor B. Administration of human IgA-IC or X-IgA to mice, killed after 6 h, resulted in glomerular deposition of IgA. Despite the presence of intense glomerular IgA deposits no C3 was detected. Collectively, these findings suggest that neither soluble nor renal localized human IgA complexes activate complement.

Animals↗
PubMed1989

Accentuated complement activation in patient plasma during the adult respiratory distress syndrome: a potential mechanism for pulmonary inflammation.

The adult respiratory distress syndrome (ARDS) represents an acute inflammatory lung disorder, characterized by both refractory hypoxemia and a mortality rate approaching 95%. Researchers have proposed that activation of the complement (C) system may play a role in the development of the pulmonary inflammation associated with ARDS. The purpose of this investigation was to determine whether complement activation occurs to a greater extent in patients with ARDS than in patients without ARDS, thereby providing a potential mechanism for the acute inflammation seen in ARDS. In this study, we assessed plasma complement activation by measuring complement activation by-products: C1rC1s-C1 inhibitor complex and C3b-P complex, generated subsequent to activation of the classical and alternative pathways, respectively, and also the terminal complement complex, formed after activation of either the classical or alternative complement pathway. Multivariate discriminant analysis revealed that these three complement activation complexes could distinguish patients with ARDS from those without ARDS (p less than 0.04). Furthermore, these three complexes provided a more sensitive discriminator of ARDS than did plasma levels of C3a desarginine (p greater than 0.30), C5a desarginine (p greater than 0.41) and total hemolytic complement activity (CH50) (p greater than 0.72). We conclude that a temporal association exists between the complement activation and the development of ARDS. Therefore, we suggest that complement activation by-products be included in the armamentarium for ARDS.

Adult↗
PubMed1987

The IgA-binding lectin jacalin induces complement activation by inhibition of C-1-inactivator function.

Jacalin, a D-galactose-specific lectin from jackfruit, interacts with human IgA and one or two other serum proteins. Incubation of jacalin with fresh human serum was shown to result in activation of the complement system. Therefore the mechanism of complement activation by jacalin was studied. Jacalin was extracted from jackfruit seeds (crude preparation) and purified to homogeneity by affinity chromatography on IgA-Sepharose to yield a pure preparation of jacalin. Both crude and pure jacalin were able to activate complement, accompanied by conversion of C3. Consumption of C1, C4 and C-1-inactivator (C-1-In) indicated involvement of the classical pathway. Aggregated IgG (AIgG) caused partial (38%) and jacalin induced complete consumption of C1-In functional activity. It was found upon Ouchterlony analysis that jacalin forms a precipitation line with purified C-1-In. In addition binding of 125I-C-1-In to jacalin-Sepharose was observed, and this binding was inhibitable by either secretory IgA or D-galactose. Next to binding of jacalin to C-1-In, jacalin was also shown to inhibit the functional activity of C-1-In. These results indicate that jacalin induces complement activation by inhibition of C-1-In function and thereby facilitates the activation of precursor C1 in either the absence or presence of low amounts of C1 activators.

Complement C1 Inactivator Proteins↗
PubMed1979

Complement activation by parasites. A review.

Activation of complement by parasites (living parasites or purified parasite antigens) is involved in several mechanisms of the host parasite relationship. In most of the experiments performed in vitro, complement activation was found to be lethal for the parasites, but sometimes it could be essential for the development of parasitemia. Both classical and alternative complement pathways may be activated by parasites; the classical pathway nearly always requires the involvement of antibodies whereas the alternative pathway is activated directly by products released by the parasites or present in their teguments. Activation of complement, especially via the alternative pathway may also be a prerequisite for cellular adherence to parasites which can then cause their death.

Animals↗
PubMed1981

Rocket immunoelectrophoresis of C4 and C4d. A simple sensitive method for detecting complement activation in plasma.

Activation of complement component C4 has recently been measured by the quantitation of C4 and C4d (a cleavage fragment of C4) by electroimmunodiffusion in gels containing specific precipitating antibodies for C4 and C4d (Rocket immunoelectrophoresis, RIE). Quantitative measurements of the complement component C4 and its fragment C4d were determined in rocket immunoelectrophoresis (RIE) and compared with measurements of total hemolytic complement activity (CH50) or concentrations of C4 as determined by single radial immunodiffusion (RID). This newly developed RIE assay shows activation of the classical complement pathway and involves electroimmunodiffusion in gels containing specific precipitating antibodies for C4 and its cleavage fragment, C4d. In 37 plasma samples, excellent correlation was demonstrated between the C4 in RIE and CH50 (r = .70) and C4 by RID (r = .87). In vivo activation of C4 was determined by measuring the ratio of C4d to C4; 21 of the plasma samples assayed had ratios greater than 1.1 indicating activation of C4. In 13 of the plasma samples there were correspondingly low CH50 values, whereas 8 had normal CH50 levels. Therefore, activation can be detected in those instances when other measurements (CH50 and C4 quantitation) are normal. Thus the RIE assay for plasma C4 activation appears to be the most sensitive method available for assessing in vivo activation of the classical pathway of complement.

Animals↗
PubMedDate not supplied

Complement activation by cigarette smoke condensate and tobacco infusion.

The capacity of tobacco infusion and cigarette smoke condensate to activate the complement pathway was investigated in vitro by hemolytic and immunological assays. Complement activity was studied using samples of normal human serum incubated at 37 degrees C with different dilutions of tobacco infusion and cigarette smoke condensate. In all mixtures containing tobacco infusion or cigarette smoke condensate at a concentration of 0.1: 1, total hemolytic complement showed an average progressive decrease of 90% and 50%, respectively, after 60 min of incubation. This decrease was associated with a decrease of both classical and alternative pathway activities. In addition, cleavage fragments of C3, C4, and factor B were identified with immunochemical analyses. This study suggests that tobacco infusion and cigarette smoke condensate are activators of complement either through the classical or alternative pathway.

Blood↗
PubMedDate not supplied

The effects of activated complement on myocardial performance in vitro.

Activated complement has been implicated in the dysfunction of several organ systems, but can it directly affect the myocardium? This possibility was studied using human right atrial trabeculae contracting isometrically "in vitro" in four solutions: Tyrode's (T), autologous arterial blood (B), plasma (P) and denaturated plasma (DP). Complement was activated by the addition of Zymosan while vehicle alone was used as control. Complement activation occurred in the blood and plasma solutions, as assessed by a significant drop in CH50 (p less than 0.05), while there was no detectable complement activity in either T or DP. Myocardial functional integrity was assessed by the change in contractile parameters with time. Subsequent resting forces, relative developed forces (DF), and rates of decay of DF were similar between muscles contracting in the four solutions. We conclude that activated complement has no direct effect on myocardial performance.

Blood↗
PubMed1979

Complement activation in acne vulgaris: consumption of complement by comedones.

Comedones, the contents of acne lesions, were shown to consume scomplement hemolytic activity in normal serum. This consumption was stimulated by the addition of serum from patients with inflammatory acne. Absorption of acne serum with Propionibacterium acnes cells removed all stimulating activity. Immunoelectrophoretic analysis of serum incubated with comedones revealed the conversion of C3 and factor B in normal serum. The addition of acne serum resulted in cleavage of C4. In serum treated with ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, only C3 and factor B were converted. This indicates that comedones may activate complement by either the classical or the alternative pathway. It is suggested that P. acnes cells in comedonal material are responsible for the complement activation.

Acne Vulgaris↗
PubMedDate not supplied

Dialysis leukopenia and hypoxemia in a patient without measurable complement activity.

We have studied complement activity, total leukocyte counts, PO2 and acid-base balance during a single hemodialysis with cuprophan membranes in a patient with hereditary angioedema and C3NeF-positive chronic membranoproliferative glomerulonephritis. Before, during and after the dialytic procedure plasma complement activity (total hemolytic complement, classical and alternative pathway activities) was not detectable and no C3-conversion occurred, while profound leukopenia (from 8,500 to 1,800 leukocytes/microliter) and hypoxemia (from 101.8 to 86 mmHg PO2) were found within 20 min from the initiation of hemodialysis. Similar results were obtained by studying the same parameters during two additional hemodialytic procedures. In vitro experiments showed that the patient's C3 could not be converted, either by cuprophan or zymosan, a specific and potent complement activator, even under optimal experimental conditions. Our data demonstrate that complement activation is not the only possible mechanism responsible for early leukopenia (as well as hypoxemia) during dialysis with cuprophan membranes.

Acid-Base Equilibrium↗
PubMed1992

Regulation of complement activity by vaccinia virus complement-control protein.

A major protein secreted by vaccinia virus-infected cells has structural similarity to the super-family of complement-control proteins. This vaccinia complement-control protein (VCP) was studied to determine how it regulates complement activation. VCP was bound by C4b and C3b and served as a cofactor with factor I in cleaving these two molecules. VCP inhibited the formation and accelerated the decay of the classical C3 convertase. It also accelerated decay of the alternative pathway convertase, although higher concentrations were apparently needed. In vitro, therefore, VCP interfered with the classical and alternative complement pathways at several steps. In vivo, this interference may increase the virulence of vaccinia virus by enabling it to escape attack by the host's complement system.

Complement Activation↗