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PubMed1984

Detection of terminal complement components in experimental immune glomerular injury.

Complement mediates glomerulonephritis by inflammatory cell-dependent and non-inflammatory cell-independent effects on glomerular permeability. The latter may involve terminal components of the complement system. We examined several models of immunologic renal injury in the rat by immunofluorescence (IF) for terminal complement components C5, C6, C7, and C8 in glomeruli using antisera to human C5-8, which cross-react with the analogous rat complement components. Rats with the heterologous and autologous phases of passive Heymann nephritis (PHN) had proteinuria and 1 to 2+ capillary wall deposits of heterologous or rat IgG, rat C3, and C5-8. Complement depletion with cobra venom factor (CVF) significantly decreased proteinuria in both models and prevented deposition of all complement components. Rats with active Heymann nephritis had similar deposits of rat IgG and C5-8. Rats with anti-GBM nephritis and aminonucleoside nephrosis had severe proteinuria which was not affected by CVF treatment and deposits of C5-8 were absent. The presence of terminal complement components in immune deposits in experimental glomerular disease correlates with a functional role for complement in mediating glomerular injury. These data support the hypothesis that the terminal complement pathway may be a major mediator of some types of immune glomerular injury.

Animals↗
PubMed1982

Interaction of rabbit spermatozoa and serum complement components.

Unheated rabbit and human sera were found to induce acrosomal loss in rabbit spermatozoa, while similar concentrations of heated sera did not. In addition, human serum did not induce acrosomal loss when pretreated with antiserum to complement component C8, suggesting that acrosomal loss in unheated serum is caused by the membrane attack complex of complement. Human serum complement anaphylatoxins did not induce acrosomal loss, although they are known to induce exocytosis of secretory granules in other cell types. When incubated directly in human or rabbit sera, rabbit spermatozoa fixed complement; i.e., reduced the potential hemolytic activity of the sera. Fixation was suppressed by adding EGTA to reduce free calcium. This indicates that rabbit spermatozoa fix complement by initiating the classical pathway to complement activation. Initiation requires the presence of cell-bound immunoglobulins and the subsequent binding of complement component C1q. Immunoglobulins were detected in detergent extracts of washed ejaculated spermatozoa by a solid-phase radioimmunoassay, and the binding of 125 I-human C1q was detected on samples of living ejaculated spermatozoa. Seminal plasma was found to inhibit complement-induced hemolysis of erythrocytes. These results suggest that, in the absence of seminal plasma, spermatozoa may activate complement where it is present in the male or female tract.

Acrosome↗
PubMed2004

Overexpression of complement inhibitor Crry does not prevent cryoglobulin-associated membranoproliferative glomerulonephritis.

BACKGROUND: Mice overexpressing thymic stromal lymphopoietin (TSLP) develop mixed cryoglobulinemia with renal disease closely resembling human cryoglobulin-associated membranoproliferative glomerulonephritis (MPGN), including glomerular deposits of immunoglobulins and complement. We assessed the effect of complement inhibition through overexpression of Crry (complement receptor-1 related gene/protein Y), which blocks the classic and alternative pathway of complement activation through inhibition of the C3 convertase, in cryoglobulinemia-associated immune complex glomerulonephritis. METHODS: TSLP transgenic mice were crossbred with animals overexpressing Crry. Mice were sacrificed after 50 days (females) or 120 days (males), and kidneys, blood, and urine were collected from seven mice of each experimental group (wild type, Crry transgenic, TSLP transgenic, and Crry/TSLP doubly transgenic). RESULTS: TSLP/Crry doubly transgenic animals demonstrated expected serum levels of Crry. Renal involvement, both in TSLP transgenic and TSLP/Crry doubly transgenic animals, was characterized by glomerular matrix expansion, macrophage influx, activation of mesangial cells, and deposition of immunoglobulins and complement. Overexpression of Crry did not result in significant improvement of renal pathology or laboratory findings. Expression of recombinant soluble Crry was confirmed by enzyme-linked immunosorbent assay (ELISA) in Crry transgenic animals. However, formation of the membrane attack complex C5b-9 as a marker of terminal active complement components and represented by glomerular C9 staining could not be inhibited in Crry transgenic TSLP mice. CONCLUSION: These results indicate that overexpression of Crry was not sufficient to prevent renal injury in TSLP transgenic mice. We suggest that the inhibitory capacity of Crry may be overwhelmed by chronic complement activation. Further studies need to address the role of complement in cryoglobulinemic glomerulonephritis before therapeutic complement inhibition can be attempted.

Animals↗
PubMed1988

Role of immunoglobulin G in killing of Borrelia burgdorferi by the classical complement pathway.

The antibody and complement requirements for killing of Borrelia burgdorferi 297 by normal human serum (NHS) and NHS plus immunoglobulin G (IgG) were examined. B. burgdorferi activated both the alternative and classical complement pathways in NHS. In NHS chelated with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus 4 mM MgCl2 (Mg-EGTA) to block classical pathway activation, consumption (activation) of total hemolytic complement, complement component 3 (C3), and C9 by B. burgdorferi was observed. Furthermore, challenge of unchelated NHS with 297 cells resulted in the consumption of C4, in addition to an increase in C3 and C9 consumption over that observed in chelated serum. In spite of complement activation, B. burgdorferi was resistant to the nonspecific bactericidal activity of NHS. The addition of human anti-B. burgdorferi IgG to NHS, however, resulted in the complete killing of 297 cells. Bactericidal activity of this serum was abrogated if NHS was immunochemically depleted of C1, indicating that killing was mediated by the classical pathway. The manifestation of bactericidal activity was accompanied by a large increase in total complement and C3 consumption over that observed in NHS alone. Under similar conditions, only a minimal increase in C9 consumption was observed. No increase in total complement consumption was observed if NHS plus anti-B. burgdorferi IgG was treated with Mg-EGTA prior to challenge. The results of these experiments demonstrate that B. burgdorferi is resistant to the nonspecific bactericidal activity of NHS, in spite of classical and alternative complement pathway activation. B. burgdorferi is sensitive to serum, however, in the presence of IgG, which mediates bacterial killing through the classical complement pathway.

Antibodies, Bacterial↗
PubMed1984

Activity of classical and alternative pathways of complement in preterm and small for gestational age infants.

Complement activity was compared in 50 low birth weight infants divided into appropriate and small for gestational age groups; the influence of birth weight and gestational age on complement development was also investigated. CH50 and kinetics (tH50) of both classical and alternative pathway activity of complement, C3, and Factor B levels were significantly higher in small for gestational age infants (classical pathway CH50, 630 HU/ml +/- 184 SD; CP tH50, 77 min +/- 47; aternative pathway CH50, 44.8 HU/ml +/- 11.3; AP tH50, 56 min +/- 43; C3, 73.98 mg/dl +/- 12.68; and Factor B, 13.17 mg/dl +/- 3.67) than in weight-matched appropriate for gestational age infants (CP CH50, 523 HU/ml +/- 152; CP tH50, 105 min +/- 49; AP CH50, 38.8 HU/ml +/- 13; AP tH50, 90 min +/- 53; C3, 58.14 mg/dl +/- 9.43; and Factor B, 9.32 mg/dl +/- 1.73). Complement values were lower in low birth weight infants than in adult controls (P less than 0.001 in all cases). All complement parameters were mainly correlated with gestational age; CH50 values of the classical and alternative pathways were also highly correlated with each other (r = 0.64; P less than 0.001). Low birth weight infants, especially preterm infants, have an important defect of complement activity. Complement factors increase gradually during gestation and intrauterine growth retardation does not affect complement development. Classical and alternative complement pathway activities have a similar development pattern.

Complement Activation↗
PubMed1999

Protection of human breast cancer cells from complement-mediated lysis by expression of heterologous CD59.

CD59, decay accelerating factor (DAF) and membrane cofactor protein (MCP) are widely expressed cell surface glycoproteins that protect host cells from the effects of homologous complement attack. Complement inhibitory activity of these proteins is species-selective. We show that the human breast cancer cell line MCF7 is relatively resistant to lysis by human complement, but is effectively lysed by rat or mouse complement. CD59, DAF and MCP were all shown to be expressed by MCF7. The species-selective nature of CD59 activity was used to demonstrate directly the effectiveness of CD59 at protecting cancer cells from complement-mediated lysis. cDNAs encoding rat and mouse CD59 were separately transfected into MCF7 cells, and cell populations expressing high levels of the rodent CD59 were isolated by cell sorting. Data show that rat and mouse CD59 were highly effective at protecting transfected MCF7 cells from lysis by rat and mouse complement, respectively. Data further reveal that rat CD59 is not effective against mouse complement, whereas mouse CD59 is effective against both mouse and rat complement. These studies establish a model system for relevant in vivo studies aimed at determining the effect of complement regulation on tumourigenesis, and show that for effective immunotherapy using complement-activating anti-tumour antibodies, the neutralization of CD59 and/or other complement inhibitory molecules will probably be required.

Animals↗
PubMedDate not supplied

False belief and sentence complement performance in children with specific language impairment.

BACKGROUND: Children with specific language impairment (SLI) have language abilities not commensurate with other cognitive abilities. This pattern makes the SLI population of interest when investigating the relationship between language and theory of mind. One view regarding this relationship is that theory of mind develops independently of language, but certain language skills are required to meet the demands of tasks used to measure theory of mind, such as false belief. Another view is that language development facilitates theory of mind development, and specifically, that mastery of sentence complement structures is necessary for false belief. AIMS: The study asked (1) if children with SLI can succeed on false belief, despite their language deficits, when the linguistic demands of the false belief task are low, and (2) if performance on sentence complement structures predicts false belief performance. METHODS & PROCEDURES: Fifteen children with SLI, 15 children matched for age and 15 children matched for language comprehension level participated in a false belief task with four conditions of differing linguistic complexity, and a test of sentence complementation understanding. Spontaneous production of sentence complements was also measured. Group differences for false belief and sentence complementation, and condition differences for false belief, were tested non-parametrically. Partial correlation analysis, log-linear analysis, and Wilcoxon-Mann-Whitney tests were used to explore relationships among the complementation and false belief measures for all children and for each group. OUTCOMES & RESULTS: Children with SLI performed similarly to age-matched peers on false belief when linguistic complexity of the task was low, and performed more poorly than age-matched peers on understanding of sentence complements. For all children, sentence complement performance was correlated with false belief (controlling for age), and those who performed well on sentence complements had higher mean rates of false belief success. Log-linear analysis showed the sentence complement-false belief relationship to hold for a condition with relatively low linguistic demands. CONCLUSIONS: The study provides evidence that children with SLI can perform at age-appropriate levels when false belief tasks are less demanding, and that mastery of sentence complementation is a predictor of false belief ability.

Child Development↗
PubMed1999

Complement activation by PEO-grafted glass surfaces.

Activation of the complement system is one way in which the human body reacts to foreign materials that come in contact with blood. Poly(ethylene oxide) (PEO) has been used quite frequently to modify biomaterial surfaces to prevent protein adsorption and cell adhesion. Despite extensive use of PEO, however, PEO-induced complement activation has not been examined before. We examined the complement activation by PEO chains grafted to glass surfaces. PEO was grafted to trichlorovinylsilane-treated glass (TCVS-glass) by gamma-irradiation using PEO homopolymer, Pluronic F108 (PF108), and PEO-polybutadiene-PEO triblock copolymer (COP5000). Complement activation was assessed by measuring the plasma C3a level. Of the three polymers grafted (PEO, PF108, and COP5000), only PF108 showed significant increases in complement activation over controls. Complement C3a production on PF108-grafted glass was linearly dependent on surface concentration of grafted PF108. The C3a concentration increased from 46 ng/mL to 316 ng/mL as the surface PF108 concentration increased from 0-0.25 microg/cm(2). Kinetics of C3a generation by PF108-grafted surfaces show that 60% of the steady state C3a concentration was generated during the first hour of plasma exposure. When the same PF108-grafted glass surface was repeatedly exposed to fresh plasma, the amount of C3a generated decreased by 70% after the first exposure. This supports the "single-hit" mechanism in complement activation. PEO homopolymer did not activate complement in bulk solution, and, thus, it appears that C3a complement activation by PF108-grafted surfaces is due to the presence of poly(propylene oxide) units. Grafting of PEO using PEO-containing block copolymers requires examination of complement activating properties of the non-PEO segment.

Biocompatible Materials↗
PubMed1997

Influence of complement on the allospecific antibody response to a primary vascularized organ graft.

The induction of antibody responses against T cell-dependent antigens has been reported to be influenced by complement. We therefore asked if the primary induction of alloantibodies against transplantation antigens, an important determinant of transplant outcome, is complement sensitive and whether this has functional implications. We transplanted rat kidney allografts into fully major histocompatibility complex-mismatched recipients, in which complement activation was inhibited by daily injection of soluble recombinant human complement receptor type 1 (sCR1). Control allograft recipients were injected with saline. Animals in the control group showed a marked antibody response against donor-specific antigens and an increase in the proportion of activated B and T splenocytes by day 5 after transplantation. Complement-inhibited rats showed a reduced level of antibody binding on target cells sharing the same histocompatibility antigens as the donor strain (p < 0.001), and a reduced level of activated splenic B (p < 0.01) and T (p < 0.01) cells. In a functional assay, the plasma of complement-inhibited rats showed reduced cytotoxic activity against donor-specific cells, and their grafts contained less bound antibody than controls. Analysis beyond 6 days was obscured due to the development of antibodies against sCR1. We conclude that complement activation facilitates the induction of the alloantibody response. Sparing of vascular injury and prolongation of graft survival, previously reported in complement-inhibited rats (Pratt J. R. et al., Am. J. Path. 1996, 149: 2055), could therefore be due to down-regulation of the B cell response as well as reduced complement-dependent cytotoxicity. Inhibition of complement may provide an ancillary approach to the prevention of allospecific antibody formation and the prolongation of allograft survival in primary kidney grafting.

Animals↗
PubMed2004

Increased sensitivity of early apoptotic cells to complement-mediated lysis.

Opsonization of apoptotic cells with complement proteins contributes to their clearance by phagocytes. Little is known about the lytic effects of complement on apoptotic cells. Sensitivity of cells treated with anti-Fas antibody (Jurkat cells), staurosporine or etoposide (Raji cells) to lysis by complement was examined. As shown here, early apoptotic cells are more sensitive to lysis by antibody and complement than control cells. More complement C3 and C9 bound to apoptotic than to control cells, even though antibody binding was similar. Enhanced killing and C3/C9 deposition were blocked by benzyloxy-Val-Ala-Asp-fluoromethylketone, a pan-caspase inhibitor. Complement-mediated lysis of early apoptotic cells was also prevented by inhibitors of caspases 6, 8, 9 or 10. In contrast, caspase inhibitors had no effect on the lysis of non-apoptotic Jurkat and Raji cells. Early apoptotic Jurkat cells were also more sensitive to lysis by the pore formers streptolysin O and melittin. Sensitivity of Jurkat Bcl-2 transfectants to lysis by complement was analyzed. Enhanced Bcl-2 expression was associated with reduced C3 deposition and lower sensitivity to complement-mediated lysis. These results demonstrate that at an early stage in apoptosis, following caspase activation, cells become sensitive to necrotic-type death by complement and other pore formers. Furthermore, they suggest that Bcl-2 is actively protecting Jurkat cells from complement-mediated lysis.

Amino Acid Chloromethyl Ketones↗
PubMed1997

Role of complement in rats injected with liposome-encapsulated hemoglobin.

Previous studies have documented that liposome-encapsulated hemoglobin (LEH) can cause a rapid and transient thrombocytopenia following intravenous injection into small animals. The present study evaluated the role of complement during the LEH-induced thrombocytopenia in rats. We have compared changes in platelet levels in the blood, platelet organ distribution, and total hemolytic complement levels following intravenous administration of LEH in control and complement-depleted rats. Changes in platelet organ distribution at various times after LEH administration were monitored by labeling autologous platelets with indium-111 (111In)-oxine and imaging the 111In-platelets with a gamma camera after reinjection. Platelet counts were determined by light-scattering methods and by following 111In radioactivity at various times after LEH administration. Platelet levels did not significantly change for the complement-depleted rats during the 60 min following an injection of LEH, whereas thrombocytopenia (40% decrease) was noted within 4 min post-LEH-injection for control rats with a gradual return to baseline circulating platelet levels within 60 min. This drop in circulating platelets was correlated with a rapid redistribution of 111In-platelets from the circulation to the lungs and liver, whereas complement-depleted rats showed no transient movement of the 111In-platelets from the circulation. Baseline complement levels of 21.6 +/- 2.2 CH50/ml for control rats and 0.2 +/- 0.1 CH50/ml for complement-depleted rats did not significantly change during the 60 min following LEH administration. This study suggests that complement must be present during LEH-induced transient thrombocytopenia, as complement-depleted rats underwent no thrombocytopenia, and that the transient LEH-induced thrombocytopenia may be associated with complement activation.

Animals↗
PubMed1984

Complement activation by cell-associated immune complexes in contact sensitivity.

Lymph node cells collected 4 days after painting the skin with picryl chloride activate the first components of the classical pathway of complement cascade, as shown by consumption of C4 of rabbit complement with total sparing of C5 and factor B activity. In contrast, lymph node cells collected 1 or 6 days after sensitization fail to do so. The ability of "4-day" cells to activate complement is inhibited by treating the cells with specific low-molecular-weight hapten, which is known to dissociate the immune complex present on the cell surface. When mouse serum was used as source of complement, a different behavior in complement activation between CBA/J and B10.D2-New/SnJ serum was observed: "4-day" cells failed to consume CBA/J serum whereas a normal complement activation was detected when B10.D2-New/SnJ serum was used. Using these two sera which differ in the level of C4, an inverse relationship between the ability of "4-day" cells to activate complement and their capacity to induce contact sensitivity when injected into the footpad of normal recipients was reported. Experiments performed using sera from C5 genetically deficient mice demonstrate that only the early complement components are involved, suggesting that membrane immune complexes are solubilized as a result of complement activation; on the other hand, membrane bound activated complement components could alter the immunizing potential of "4-day" cells.

Animals↗
PubMed1988

The complement system in atherosclerosis.

Complement is a term referring to a collection of plasma proteins, specific cellular receptors and cell surface regulatory molecules. Activation of the complement system to completion results in the formation of C5b-9 terminal complexes. These complexes have been observed in human atherosclerotic lesions by immunohistochemistry. Although the structure(s) which activate complement in lesions have not been defined, cholesterol and oxysterols exhibit this property in vitro. Endothelial cell damage leads to complement activation and endothelial cells overlying atherosclerotic lesions have been observed to contain C3 and C5b-9 antigens. Cardiac myocytes stain for complement proteins (C3, C4 and C5b-9) following myocardial infarction. Infarct size and extent of inflammatory cell infiltrates are diminished by decomplementation prior to experimentally-induced myocardial ischemia. Following myocardial infarction and ulceration of atherosclerotic lesions in human patients there is an increase in circulating complement activation products and a decrease in the level of native C1 through C4 proteins. Thus, it appears that complement plays a role in atherogenesis and its sequelae. Little is known however, about the pathophysiological effects complement activation products exert on lesion development, for example through modulation of macrophage functions, or how complement activation is regulated in lesions. Implications for complement in atherogenesis are discussed.

Animals↗
PubMed2006

Complement inhibitors selectively attenuate injury following administration of cobra venom factor to rats.

Systemic activation of complement is a pathophysiological response common to severe disturbances such as hemorrhagic shock, major burn injury and sepsis. Intravenous infusion of cobra venom factor (CVF) has been used as an animal model of acute respiratory distress syndrome (ARDS), and reliably and selectively induces rapid intravascular activation of the complement system, leading to acute organ damage. In the present study, we have used different complement inhibitors to investigate the roles of complement products in CVF-induced responses in the rat. Rats were treated with either a C5a receptor antagonist (C5aRA, AcF-[OP(d-Cha)WR], 1 mg/kg i.v. or 10 mg/kg p.o.), a C3a receptor antagonist (C3aRA, N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine, 0.1 mg/kg i.v.) or a convertase inhibitor, rosmarinic acid (RMA, 10 mg/kg i.v.), prior to CVF-induced complement challenge. Intravenous CVF resulted in hallmark events evident in the development of ARDS, including systemic neutropenia followed by neutrophil migration to the lung and bronchoalveolar vascular leakage, blood pressure alterations, and an increase in TNFalpha levels in both serum and bronchoalveolar lavage fluid. These hemodynamic changes were differentially inhibited by antagonism of C5a receptors, C3a receptors or by inhibition of the entire complement cascade using RMA. This evidence strongly implicates complement factors in the development of lung injury associated with systemic complement activation and identifies complement inhibition as a potential therapeutic target for acute syndromes such as ARDS and other severe systemic shock states mediated by activation of complement.

Administration, Oral↗
PubMed2004

Initiation of complement activation following oxidative stress. In vitro and in vivo observations.

Ischemia and reperfusion of organs/tissues induce a state of inflammation that can lead to tissue injury. Focus on development of effective therapeutics based on sound pre-clinical work and the role of leukocytes in models of human disease has not lead to a successful clinical trial for anti-leukocyte technologies. For the past >30 years, it has been known that complement activation plays a role in the inflammation and tissue injury associated with ischemia/reperfusion (I/R) injury. In the last 10 years, several complement inhibitors have made their way from the bench to bedside. Will a complement inhibitor eventually be approved for clinical treatment of I/R type diseases? What pathway(s) are involved in I/R injury, and what role do they play? What specific complement components are needed for resolution of inflammation and what components need to be inhibited to decrease tissue injury? This short review will focus on the current state of the art knowledge about complement, complement pathways, complement components and several promising clinical biologics that inhibit complement activation. This review is not a complete review of complement in ischemia/reperfusion injury, but it raises important questions about the role of complement, its pathways and the current knowledge in the area of ischemia/reperfusion injury.

Animals↗
PubMed2004

Primitive complement system--recognition and activation.

The complement system, composed of more than 30 serum and cell surface components, is collaborating in recognition and elimination of pathogens as a part of both the innate and acquired immune systems. The two collagenous lectins, mannose-binding lectin (MBL) and ficolins, are one of the pattern recognition molecules acting in innate immunity and upon recognition of the pathogens, they trigger the activation of the lectin complement pathway through attached serine proteases (MASPs). A similar lectin-base complement system, consisting of the lectin-protease complex and C3, is present in ascidians, our closest invertebrate relatives and functions in an opsonic manner. On the other hand, ongoing genome projects in both vertebrates and invertebrates revealed that most domains used by mammalian complement components are found in both protostomes and deuterostomes. However, the unique combinations of them as found in mammalian complement components are present only in deuterostomes, indicating the deuterostome origin of the complement system. Unexpectedly, the complement system of an invertebrate deuterostome, ascidian, shows a similar level of complexity as that of mammals, suggesting that expansion of complement genes by gene duplications occurred independently both in the ascidian and vertebrate lineages. Although most characteristic domain structures of the mammalian complement components are found in ascidians, detailed evolutionary analysis casts doubt on their mutual reactivity in several points. Thus, another integrative step seems to have been required to establish the modern complement system of higher vertebrates.

Animals↗
PubMed2001

Autoantibodies to complement components.

The complement system is a major component of innate immunity. Under normal conditions the contribution of the complement system is beneficial, but when inappropriately activated it may cause damage to the host and under certain conditions it may even be the target of an autoantibody response. Autoantibodies directed against individual complement components, convertases, complement regulators and complement receptors have been described. The presence of autoantibodies in individuals may be associated with manifestations of disease, but only for some autoantibodies have clear causal relations been described. Autoantibodies against complement components can even be present in healthy individuals, indicating that the development of pathology most likely requires the simultaneous action of multiple processes. Since autoantibodies against complement components may cause depletion of circulating complement levels, leading to a secondary complement deficiency, it is imaginable that this process leads to an increased susceptibility to infections. In the present review, we describe autoantibodies against complement components and their subsequent effects.

Autoantibodies↗
PubMed1999

Complement activation by oxidatively modified low-density lipoproteins.

BACKGROUND: Oxidatively modified low-density lipoproteins (LDLs) have been implicated in the pathogenesis of atherosclerosis and are found in human vascular lesions. There is increasing evidence that complement activation may also play a role in atherogenesis. Activated complement proteins have been demonstrated to be present in early atherosclerotic lesions, and lipids isolated from lesions have been shown to activate complement, hence their designation as lesion complement activator (LCA). The question now arose whether oxidized LDLs would also activate complement. MATERIAL AND METHODS: The complement-activating capacity of a lesion complement activator preparation and of minimally as well as heavily oxidized LDL was investigated by measuring SC5b-9 formation in normal human serum. In addition, C3 conversion was followed using two-dimensional immunoelectrophoresis. RESULTS: Minimally and heavily oxidized LDL generated small but significant amounts of SC5b-9 (7.9 microgram mL-1, SD 3.5, and 10.8 microgram mL-1, SD 1.2, respectively; n = 6) compared with native LDL (3.3 microgram mL-1, SD 1.4; P < 0.05), whereas LCA generated substantially larger amounts of the terminal complex (32.0 microgram mL-1, SD 3.2). Both oxidized LDL preparations caused only minor C3 conversion. CONCLUSIONS: These findings show that oxidation does not confer relevant complement-activating properties on LDL, suggesting that the lesion complement activator is not directly related to oxidized LDL. Oxidized LDL is probably of minor importance for complement activation in atherosclerotic lesions.

Arteriosclerosis↗