Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “complementation”

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

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

At least 1,009 records · Page 56Linked to original sources
PubMed1998

Complement activation by diesel exhaust particles (DEP).

The effect of diesel exhaust particles (DEP) on the hemolytic activity of human serum complement was investigated. Previous treatment of human serum with DEP extracts at 37 degrees C decreased the hemolytic activity of human serum complement dose dependently, to 20% of its original value. This decrease in complement activity by DEP extracts was observed with previous incubation at 37 degrees C but not at 4 degrees C. A decrease in complement activity was observed after previous incubation at 37 degrees C in the presence of EGTA/Mg but not in the presence of EDTA, indicating that the alternative pathway of the complement system had been activated by DEP extracts. Activation of the complement system by DEP extracts was further demonstrated by observation of the cleavage of the third component of the complement (C3) in serum to C3b with immunoelectrophoresis using goat anti-human C3 antiserum. This cleavage of C3 was similarly observed in the presence of EGTA/Mg, indicating the activation of the alternative pathway of the complement system by DEP extracts. These results indicate that DEP can activate the alternative pathway of the complement system, resulting in a decrease in the hemolytic activity of complement and in the production of biologically active degradation products of complement proteins such as C3a. The biological significance of the activation of the complement by DEP in the alveolus is discussed in relation to the influx of neutrophiles.

Animals↗
PubMed2006

Measuring human complement activation by HLA antibodies.

CONTEXT: The clinical significance of HLA antibodies in transplantation depends on their ability to activate complement, which is measured by the standard complement-dependent cytotoxicity test. Recent reports indicate that C3b measurement on target cells may be a better indicator of human complement activation than standard cytotoxicity. OBJECTIVE: To determine the characteristics of the test, the role of other complement components, and the potential influence of the patient's own complement activity. DESIGN: The T-cell deposition of multiple complement components triggered by HLA alloantibodies was evaluated by flow cytometry using normal human serum as the source of complement. Complement activity in patients' sera was measured after activation with a standard antibody. RESULTS: When HLA antibodies activate complement, C3b deposition is usually highest, followed by that of C4b and C5b. Deposition of C1q, C3d, iC3b, or C5b-9 was low or undetectable in this study. The C5 was activated only when relatively high levels of C3b were present. There was a critical concentration of antibody, unique for each patient, below which activation of C3 declined abruptly. The complement activity in the serum of candidates for liver, heart, and lung transplantation that was tested with a standard antibody was similar to normal serum. In contrast, kidney transplant candidates exhibited higher complement activity. Unexpectedly, serum C3 activity was retained for at least 72 hours after collection. CONCLUSIONS: Measurement of C3b, and in some instances C4b or C5b, offers a better definition of the ability of HLA antibodies to activate human complement than tests that are in current use. The results provide a necessary baseline to conduct clinical correlation studies.

Complement Activation↗
PubMed2006

Recent advances on the complement system of teleost fish.

The complement system plays an essential role in alerting the host of the presence of potential pathogens, as well as in their clearing. In addition, activation of the complement system contributes significantly in the orchestration and development of an acquired immune response. Although the complement system has been studied extensively in mammals, considerably less is known about complement in lower vertebrates, in particular teleost fish. Here we review our current understanding of the role of fish complement in phagocytosis, respiratory burst, chemotaxis and cell lysis. We also thoroughly review the specific complement components characterized thus far in various teleost fish species. In addition, we provide a comprehensive compilation on complement host-pathogen interactions, in which we analyze the role of fish complement in host defense against bacteria, viruses, fungi and parasites. From a more physiological perspective, we evaluate the knowledge accumulated on the influence of stress, nutrition and environmental factors on levels of complement activity and components, and how the use of this knowledge can benefit the aquaculture industry. Finally, we propose future directions that are likely to advance our understanding of the molecular evolution, structure and function of complement proteins in teleosts. Such studies will be pivotal in providing new insights into complement-related mechanisms of recognition and defense that are essential to maintaining fish homeostasis.

Animals↗
PubMed2005

Evolutionary history of orthopoxvirus proteins similar to human complement regulators.

Orthopoxviruses include many important pathogens such as variola major virus, camelpox, buffalopox, monkeypox, cowpox, and variola minor viruses. This group of viruses also includes vaccinia virus, which is extensively used in human vaccine development. Genomes of orthopoxviruses encode proteins with sequences similar to human regulators of complement activation (RCA) that contain tandem short consensus repeats (SCRs). We employed phylogenetic tree analysis to evaluate the structural relationships among SCRs of orthopoxvirus RCA-like proteins and those of human complement regulators. The human complement RCA proteins analyzed were factor H (FH), C4 binding protein alpha chain, membrane cofactor protein (MCP), decay accelerating factor (DAF), and complement receptors type 1 (CR1) and 2 (CR2). Sequences of key poxvirus regulators of complement activation, vaccinia virus complement control protein (VCP), smallpox inhibitor of complement enzymes (SPICE), and cowpox inflammation modulatory protein (IMP) were similar to SCRs 1 through 5 of C4 binding protein, alpha chain, and they were also clustered with other homologous repeats of MCP, DAF, CR1, CR2, and FH. Phylogenetic clustering of RCA sequences suggested that poxvirus complement regulators VCP, SPICE, and IMP arose from a single ancestral sequence that shared similarity with all human regulators of complement activation. Any changes in poxvirus complement regulators leading to the enhancement of their ability to regulate complement activation likely resulted from new mutations in the viral lineages.

Antigens, CD↗
PubMed1997

Effect of body weight and caloric restriction on serum complement proteins, including Factor D/adipsin: studies in anorexia nervosa and obesity.

Complement plays important roles in host immune defences, and recent studies suggest that adipose tissue is an important site of production for some complement proteins. Starvation has been associated with low complement levels, but studied populations have usually had concomitant opportunistic infections or other conditions which might affect complement levels. To determine the impact of body weight and changes in body weight on serum complement, we investigated levels of complement proteins in otherwise healthy patients with a wide range of body weights, including patients with anorexia nervosa before and after treatment, obese dieters before and after weight loss, and normal weight controls. We found that complement proteins of the alternative pathway (C3, B, and D), alternative pathway haemolytic activity (AP50) and the inhibitors H and I were low in starving anorectics and normalized with weight gain. C3a levels were comparable in anorectics at low weight and after weight gain, indicating that low serum complement levels were attributable to hypoproduction and not complement cascade activation with consumption. Further, levels of C3, B, AP50, H and I, but not D, were higher than controls in obese patients and decreased toward normal after weight loss. Overall, percentage of ideal body weight, changes in body weight, and serum transferrin were each highly correlated with serum levels of complement proteins. We conclude that levels of alternative pathway complement components are determined in part by factors that influence body weight and by weight changes, possibly due to changes in production in adipose tissue or at other sites.

Adult↗
PubMed1982

Complement consumption gonococcal peptidoglycan.

Purified peptidoglycan (PG) obtained from Neisseria gonorrhoeae was tested for the ability to consume complement in normal human sera. Sonicated PG (S-PG), a heterogeneous mixture of soluble fragments (molecular weight, greater than 10(6)), as well as intact (insoluble) PG, reduced the level of whole hemolytic complement in a pool of four human sera. The minimal concentration of S-PG required for this activity was approximately 500 micrograms of S-PG per ml of serum. Complete lysozyme digestion of S-PG, yielding PG fragments of less than 10(4) molecular weight, eliminated complement-consuming activity. S-PG-mediated complement consumption resulted in depletion of the individual complement components C4 and C3. Consumption of complement did not occur when C4-deficient human serum or normal human sera treated with Mg2+-(ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid to specifically impair classical complement pathway activity were used. The addition of rabbit anti-PG antibody greatly enhanced gonococcal PG-mediated complement consumption. Together, the data suggested that gonococcal PG-mediated complement consumption occurred via the classical complement pathway, was dependent on the presence of anti-PG antibody, and required glycosidically linked polymers of PG. Individual human sera varied widely in the extent of gonococcal PG-mediated reduction of complement levels, presumably a reflection of either different amounts of natural antibody to gonococcal PG, different levels of human PG hydrolase(s) capable of degrading PG to inactive fragments, or both.

Antibodies, Bacterial↗
PubMed2001

Systemic complement depletion diminishes perihematomal brain edema in rats.

BACKGROUND AND PURPOSE: The complement cascade is activated after experimental intracerebral hemorrhage (ICH). It remains unclear, however, whether depleting the complement system will improve injury resulting from ICH. This study investigated the effects of systemic complement depletion on brain edema formation after ICH. METHODS: Fifty-six pentobarbital-anesthetized Sprague-Dawley rats were used. Treatment animals were complement-depleted with cobra venom factor (CVF) (intraperitoneally). Control rats received an equal volume of saline injection (intraperitoneally). In both treatment and control rats, autologous blood (100 microL) was infused stereotaxically into the right basal ganglia. Rats were killed 2, 24, or 72 hours later for brain water, ion, and tumor necrosis factor-alpha (TNF-alpha) measurements, for Western blot analysis, and for immunohistochemical studies. Brain edema was quantitated by wet/dry weight. TNF-alpha levels were measured by enzyme-linked immunosorbent assay. Western blot analysis was applied for C9 semiquantification. Immunohistochemistry was used to detect complement C3d, C5a, C9, and myeloperoxidase. RESULTS: Perihematomal brain edema was reduced by systemic complement depletion at 24 hours (78.8+/-0.6% versus 81.5+/-0.8% in control, P:<0.01) and 72 hours (81.5+/-1.5% versus 83.6+/-0.9% in control, P:<0.05), while cerebellar water content was unaffected (78.2+/-0.3% versus 78.0+/-0. 1%). Complement depletion reduced TNF-alpha production 2 hours after ICH. Immunocytochemistry showed that complement depletion significantly reduced perihematomal C9 deposition, C3d production, and the number of C5a- and myeloperoxidase-positive cells. CONCLUSIONS: Complement depletion by CVF attenuates brain edema in ICH, indicating that complement activation plays an important role in ICH-induced brain edema. Preventing complement activation may be effective in the treatment of ICH.

Animals↗
PubMed2001

Interaction of poly(2-acrylamido 2-methylpropane sulfonate)-grafted polystyrene beads with cationic complement proteins.

Influence of various biomaterials on the complement system in serum has been intensively studied by many research groups, since activation of the complement pathway in vivo has been known to give rise to some pathological conditions, such as inflammation and anaphylaxis. Much effort has been devoted to develop new materials that do not activate or deteriorate the complement system. The present work is aimed at revealing the mode of reactions of anionic poly(2-acrylamido 2-methylpropane sulfonate) grafted on polystyrene bead (PAMPS-g-bead) with serum complement. Complement activity assay, determination of complement proteins levels, and immunoblot analysis were carried out for sera pretreated with PAMPS-g-beads. The results clearly showed that, when PAMPS-g-beads were incubated with serum, those beads adsorbed several complement proteins, i.e. C1q, factor D, factor P, C6, and C8, but the generation of activation fragments of complement components was not observed. Especially, factor D was most effectively removed from serum, resulting in potential inhibition of the alternative pathway. A larger amount of PAMPS-g-beads was needed to decrease the serum CH50 level. That may be caused by removal of C6. Although some polyanions, such as dextran sulfate, were reported to activate the complement system, the obtained results indicate that the PAMPS-g-bead is not an activator of the complement pathway, but acts as an adsorbent of complement components. One possible clinical application of the PAMPS-g-beads is adsorption of serum factor D by extracorporeal treatment of patients with renal failure with a high level of factor D, because the increased quantity of factor D in serum may cause consistent activation of the alternative pathway.

Biocompatible Materials↗
PubMed1992

Inhibition of equine complement activity by polysulfated glycosaminoglycans.

The ability of polysulfated glycosaminoglycans (PSGAG) to inhibit the complement cascade was evaluated. The role of complement in inflammation and infection has been well documented. Inhibition of the complement cascade by PSGAG could explain why intra-articularly administered PSGAG diminish diarthrodial joint inflammation and potentiate septic arthritis in horses. Hemolytic complement testing was performed to evaluate the effect of PSGAG on the equine classical and alternate pathways of complement, using rabbit erythrocytes as the target cells. Concentration of PSGAG between 0.2 mg/ml and 0.6 mg/ml significantly (P less than 0.05) inhibited equine complement in dose-related fashion. Further increase in complement inhibition was not observed at PSGAG concentration greater than 0.6 mg/ml. Difference was not apparent in the extent of inhibition of complement from each of the 4 horses tested. Polysulfated glycosaminoglycans appeared to inhibit the classical and alternate complement pathways equally, indicating possible effect on complement components common to both pathways. Heat inactivation of complement function completely inhibited (P less than 0.01) the hemolytic activity of the serum from all horses.

Animals↗
PubMed2005

Common variable immunodeficiency and the complement system; low mannose-binding lectin levels are associated with bronchiectasis.

The importance of the innate immune system, including mannose-binding lectin and the complement system, in common variable immunodeficiency is unclear. The objective of this study was to evaluate mannose-binding lectin and the complement system in relation to clinical and immunological parameters in patients with common variable immunodeficiency. Circulating levels of mannose-binding lectin, complement components, complement activation products and functional capacity of complement pathways were correlated to clinical features within 71 patients and compared with 30 healthy controls. The main findings were; the patients had signs of increased complement activation significantly associated with signs of autoimmunity and immunological hyperactivity; there were no signs of deficiencies of the classical and alternative complement pathways in the patient group; the prevalence of lectin pathway deficiency was the same in patients and controls, but patients with increased frequency of lower respiratory tract infections or bronchiectasis had lower capacity of the lectin pathway than patients without these features (P = 0.002 and 0.004, respectively); the serum concentration of mannose-binding lectin was inversely correlated to the frequency of lower respiratory tract infections (P = 0.002) and bronchiectasis (P = 0.01). We conclude that patients with common variable immunodeficiency have no increased frequency of complement deficiencies but signs of increased complement activation. Our findings suggest that mannose-binding lectin and the lectin complement pathway may protect against lower respiratory tract infection and bronhiectasis in patients with common variable immunodeficiency.

Adult↗
PubMed1987

A complement-resistant HeLa cell line (T638) is blocked at the step of C3 deposition.

A complement-resistant line of HeLa cells (T638) was derived by serial passage of complement-susceptible HeLa cells in anti-beta 2-microglobulin (b2m) antiserum and complement. The T638 line maintained stable complement resistance when passed for an additional 1500 generations in the absence of antiserum and complement. T638 cells expressed equivalent levels of cell-associated b2m as did the parent HeLa cell line. Furthermore, T638 cells were resistant to killing by complement and anti-HeLa antiserum with specificity for molecules other than b2m. These results indicate that the resistance of T638 cells does not simply reflect loss of anti-b2m binding antigens. We next investigated the mechanism of resistance of T638 cells to complement-mediated killing. Antibody-sensitized HeLa and T638 cells both consumed CH50 activity completely from normal human serum; cytotoxicity was not mediated via the alternative complement pathway. HeLa and T638 cells caused equivalent utilization of C4 from normal human serum in the presence of antibody. Consumption of C2, greater with T638 than with HeLa cells during incubation in serum, was complete when cells bearing purified C1 and limited C4 were incubated with C2. T638 cells bound more 3H-C4 than HeLa cells during incubation in serum, but binding of 3H-C3 by T638 cells was fourfold to fivefold less than by HeLa cells. Finally, we investigated the rate of decay in the capacity of C142 on HeLa and T638 to cleave and deposit 3H-C3. The T1/2 for decay of C142-mediated binding of 3H-C3 on HeLa was 3.9 min, whereas minimal C3 deposition was detected on T638 cells at all time points. These results show that T638 cells evade complement-mediated lysis despite activating early components of the classical complement pathway. The mechanism of resistance is a failure to form an effective C3 convertase.

Antibodies↗
PubMed1993

Murine complement-mediated immune clearance dysfunction is associated with the lymphoproliferative (lpr) gene.

Using a branched series model of immune clearance and an iterative curve fitting process, we have previously demonstrated abnormal in vivo clearance of opsonized erythrocytes in autoimmune MRL-lpr/lpr mice. This technique allows simultaneous evaluation of four rate constants governing both complement- and Fc-mediated clearance; i.e., complement-mediated sequestration (k1), C3b deactivation and release (k2), complement-dependent phagocytosis (k4), and Fc gamma-mediated sequestration and phagocytosis (k3). To evaluate genetic factors which may contribute to abnormal clearance in MRL-lpr/lpr mice, serial clearance studies were performed in congenic MRL-(+/+) mice, as well as in several mouse strains homozygous for the lymphoproliferative gene; i.e., BALB/c-lpr/lpr and C57BL/6-lpr/lpr mice. Rate data were obtained from mice 3 months through 12-18 months of age, and mean rate constant values compared to control BALB/c and/or C57BL/6 mice. Clearance of opsonized cells in MRL-lpr/lpr mice was characterized by both abnormal complement and Fc gamma receptor function with decreased complement-mediated sequestration, complement-dependent phagocytosis, and Fc gamma-mediated sequestration and phagocytosis. In contrast, abnormal clearance in congenic MRL-(+/+) mice was characterized by decreased Fc gamma-mediated sequestration and phagocytosis (P < 0.0001) only. Both complement-mediated sequestration and complement-dependent phagocytosis were significantly decreased in BALB/c-lpr/lpr and C57BL/6-lpr/lpr mice (P < 0.0001), with the pattern and magnitude of abnormal complement clearance kinetics similar to that occurring in MRL-lpr/lpr mice and contrasting with normal complement-mediated clearance in control BALB/c and C57BL/6 mice. Since decreased complement-mediated clearance was observed in three differing strains of mice homozygous for the lymphoproliferative gene, these data suggest that clearance of opsonized cells in mice is in part genetically determined, and that there may be a specific association between complement-mediated clearance dysfunction and the murine lymphoproliferative gene.

Animals↗
PubMed1995

Activation of complement by human hemoglobin and by mixtures of hemoglobin and bacterial endotoxin.

Purified human hemoglobin is being developed as an alternative to transfusions of homologous erythrocytes. However, toxicity associated with infusion of hemoglobin has limited the development of this resuscitation fluid. Some observed toxicities, including activation of the complement cascade, have been associated with contamination of hemoglobin solutions by bacterial endotoxin. Recent studies have demonstrated complex formation between hemoglobin and endotoxin, and have documented a resultant increase in the ability of endotoxin to activate coagulation, stimulate tissue factor production by human peripheral blood mononuclear cells, and stimulate tissue factor activity and protein synthesis in cultured human endothelial cells. The process of hemoglobin enhancement of endotoxin toxicity suggests a possible mechanism by which the consequences of endotoxin contamination of hemoglobin solutions, including complement activation, could be magnified. Therefore, we studied the potential of hemoglobin to either fix complement directly, or modify the ability of endotoxin to fix complement. Human crosslinked and native hemoglobins, at concentrations between 0.2 mg/ml and 3 mg/ml, were shown to fix complement. Complement fixation by hemoglobin was identical in normal human serum or in factor B-depleted serum, suggesting that fixation occurred via the classical pathway of complement activation. Complement fixation then was examined with a battery of smooth and rough endotoxins tested in the absence and presence of hemoglobin. Addition of hemoglobin to a solution of a rough Salmonella endotoxin partial structure, from which a single fatty acid had been hydrolyzed from the lipid A portion of the macromolecule, resulted in decreased efficiency of complement fixation. However, addition of hemoglobin had little or no effect on the intrinsic complement fixing abilities of eight other smooth endotoxins, rough endotoxins, or endotoxin partial structures. Our results demonstrated the ability of hemoglobin to fix complement at hemoglobin concentrations which would be achieved during infusion for resuscitation, but failed to demonstrate a reproducible effect of hemoglobin on the activation of complement by endotoxin.

Bacterial Toxins↗
PubMed1999

Initial characterization of the complement activating compounds in extracts of smokeless tobacco.

Aqueous extracts of smokeless tobacco (ST) have been shown to be potent activators of complement. However, the mechanisms by which smokeless tobacco activates complement are not well understood. This study was undertaken to identify the complement activating compounds in ST extracts. The approximate molecular size of the activating agent(s) in smokeless tobacco was determined by dialyzing aqueous extracts of loose leaf chewing tobacco (1S1), dry snuff (1S2), and moist snuff (1S3). Following dialysis (total dilution effect of 1:10(9)), using a membrane with a molecular weight retention limit of 12-14 kDa, all extracts retained full capacity to activate serum complement as determined by a hemolytic assay. Fractionation of the extracts by gel filtration chromatography revealed that the complement activating agents in ST were high molecular weight compounds that eluted between 400 kDa and the void volume (1500 kDa) of a Sephacryl S300 column. The high molecular weight complement-activating peak was isolated and found to be a more potent complement activator than the unfractionated extract. The chemical nature of the complement activating compounds was determined by subjecting the extracts to boiling for 30 min, an organic extraction with chloroform/methanol 2:1, or treatment with a DNAse/RNAse enzyme cocktail. None of these treatments destroyed the capacity of ST extracts to activate complement, suggesting that the activating agents may be carbohydrate-like. Finally, an extraction protocol designed to remove polyphenols significantly diminished the complement activating capacity of the ST extracts. These results clearly demonstrate that the complement activating substances in smokeless tobacco extracts may be large (>400 kDa) polyphenol-containing compounds (i.e. tannins). Identification of this agent(s) will be important for distinguishing the mechanism of smokeless tobacco-induced complement activation.

Complement Activation↗
PubMed1996

Differential expression of complement components in human fetal and adult kidneys.

Various studies have shown that complement components are synthesized by renal cells and that mRNA for a number of complement components is detectable in renal tissue. The present study shows that complement proteins are present both in fetal and adult human kidneys. The localization of the complement components was compared with the localization of other proteins for which specific expression in defined renal cell types is known from the literature. In adult human kidneys C3, factor B and factor H were detected in the mesangial area by immunohistochemistry, whereas C2 and C4 were present in the proximal tubuli. In fetal kidneys C3 and factor B were expressed in glomeruli of kidneys of 11 weeks of gestation. In kidneys of 13 to 19 weeks of gestation no staining for C3 was found in the glomerulus, whereas for factor B glomerular staining was found in all fetal kidneys examined. Factor B was also detected in fetal tubuli and in the interstitium. Factor H was expressed in fetal tubuli starting at 13 weeks of gestation. For both C3 and C2 weak tubular staining was found in all fetal kidneys investigated. C4 could not be detected in any of the fetal kidneys. While not all the complement proteins investigated were detectable by immunohistochemistry, by RT-PCR analysis, mRNA expression for C3, factor B, factor H, C2 and C4 was found in all adult and fetal renal tissue. The finding of mRNA for the complement components in the fetal and the adult kidneys indicates that local synthesis of complement occurs both in the adult and in the fetal kidney. Next to the in situ expression of complement components in fetal kidneys the synthesis of complement proteins in vitro by fetal renal cells was investigated. Four different primary mesangial cell lines were shown to synthesize all complement proteins investigated. Although a specific role for complement during the development of the kidney is not known, it is possible that certain complement components may play a role during renal differentiation.

Adult↗
PubMed2001

Induction of complement sensitivity in Escherichia coli by citric acid and low pH.

AIMS: The lytic functions of the complement system play an important role in the control of Gram-negative infections. Complement-resistant Escherichia coli LP1395 (O18) grown under normal conditions can survive the bactericidal action of complement present in human serum. Towards elucidating the mechanisms of complement resistance, the resistance of E. coli LP1395 grown under conditions of low pH and in the presence of citric acid was tested. METHODS AND RESULTS: E. coli LP1395 becomes sensitive to complement after growth in the presence of citric acid at pH 5. Complement resistance could be restored when the cells were transferred to pH 7 media. However, this recovery was greatly impaired when the cells were transferred to pH 7 media with chloramphenicol. This implies that protein synthesis may be involved in complement resistance. The cells exposed to citric acid at pH 5 showed no indication of a generalized outer membrane (OM) permeability when compared with those grown under normal conditions in terms of sensitivity to lysozyme, uptake of lipophilic dye, or sensitivity to a number of antibiotics. CONCLUSION: Complement-resistant LP1395 may acquire a sensitivity to complement due not to a generalized disruption of the OM barrier, but possibly to the alteration of the activity of one or more normal complement resistance factors. SIGNIFICANCE AND IMPACT OF THE STUDY: The elucidation of the mechanisms of complement resistance of Gram-negative pathogens would bring important information about bacterial infections. Complement resistance factors could also be potential targets in antimicrobial therapies.

1-Naphthylamine↗
PubMed1997

Vitronectin-binding staphylococci enhance surface-associated complement activation.

Coagulase-negative staphylococci are well recognized in medical device-associated infections. Complement activation is known to occur at the biomaterial surface, resulting in unspecific inflammation around the biomaterial. The human serum protein vitronectin (Vn), a potent inhibitor of complement activation by formation of an inactive terminal complement complex, adsorbs to biomaterial surfaces in contact with blood. In this report, we discuss the possibility that surface-immobilized Vn inhibits complement activation and the effect of Vn-binding staphylococci on complement activation on surfaces precoated with Vn. The extent of complement activation was measured with a rabbit anti-human C3c antibody and a mouse anti-human C9 antibody, raised against the neoepitope of C9. Our data show that Vn immobilized on a biomaterial surface retains its ability to inhibit complement activation. The additive complement activation-inhibitory effect of Vn on a heparinized surface is very small. In the presence of Vn-binding strain, Staphylococcus hemolyticus SM131, complement activation on a surface precoated with Vn occurred as it did in the absence of Vn precoating. For S. epidermidis 3380, which does not express binding of Vn, complement activation on a Vn-precoated surface was significantly decreased. The results could be repeated on heparinized surfaces. These data suggest that Vn adsorbed to a biomaterial surface may serve to protect against surface-associated complement activation. Furthermore, Vn-binding staphylococcal cells may enhance surface-associated complement activation by blocking the inhibitory effect of preadsorbed Vn.

Animals↗
PubMed1988

Complement is not involved in monocrotaline pyrrole-induced pulmonary injury.

Monocrotaline pyrrole (MCTP) causes pulmonary vascular injury, pulmonary hypertension, and right ventricular hypertrophy in rats. The mechanisms by which MCTP causes lung injury are not known. After treatment with a moderate dose of MCTP, several days pass before major lung injury is detected, thus suggesting that the damage is caused indirectly. Since activation of the complement system can cause lung injury, it was of interest to test whether complement activation may be important in lung injury due to MCTP. Accordingly, rats were given a single dose of MCTP (3.5 mg/kg iv), and serum hemolytic complement activity was measured at several times after rats were treated. Neutrophil aggregometry also was used to determine whether complement activation products could be detected in serum after MCTP was given in vivo. The effect of complement depletion on MCTP-induced pulmonary injury was tested by cotreating rats with purified cobra venom factor and MCTP. MCTP treatment did not cause detectable complement activation in vivo, and complement depletion did not protect rats from lung injury. The direct effect of MCTP on serum complement also was tested by exposing fresh rat serum to MCTP in vitro and measuring serum complement activity. MCTP decreased serum hemolytic complement activity in vitro, but it did not interfere with subsequent zymosan-induced activation of complement. These results suggest that complement does not play a role in the development of major lung injury that occurs several days after treatment of rats with MCTP.

Animals↗