Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement Inactivator Proteins”

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 613 records · Page 34Linked to original sources
PubMed1980

Demonstration of a complement-dependent migration inhibitory activity in normal guinea pig serum.

A cell migration inhibitory effect was evidentiated in normal guinea pig serum as compared with heat inactivated serum. Granulocytes when used as target showed a greater sensitivity to this effect than lymphomonocytes or macrophages. The migration inhibitory activity of GPS is abrogated or decreased by using complement destroying agents such as: heating at 56 degrees C for as little as 5 min, absorption on immune complexes in presence of calcium, on zymosan, on Sephadex G-50 or by adding EDTA or heparin to culture medium. The GPS dialysation fractions while exhibiting neither complement haemolytic effect nor migration inhibitory activity when tested alone, restored these functions by recombination. Absorption of GPS on homologous blood cells abrogated the migration inhibitory effect but retained the complement haemolytic function. When GPS absorbed on homologous blood cells mixed 1:5 with heat-inactivated serum (5 min at 56 degrees C), the migration inhibitory activity was regained, suggesting that the complement factors from the first sample were necessary for manifestation for the migration inhibitory activity from the heat-inactivated serum.

Animals↗
PubMed1998

Complement inhibition by FUT-175 and K76-COOH in a pig-to-human lung xenotransplant model.

Two complement inhibitors, FUT-175 (FUT) and K76-COOH (K76), were studied as single agents in an ex vivo, in situ model of pig lung rejection by human blood. Pulmonary toxicity (primarily increased pulmonary vascular resistance [PVR]) was seen with FUT at a dose which inhibited complement in vitro (0.4 mg/ml); a lower dose (0.1 mg/ml) was therefore used. K76 had little apparent toxicity at a dose which inhibited complement in vitro (6 mg/ml), but activated complement, leading to C3a elaboration. Efficacy was then assessed by 1) deposition of complement pathway components in the lung and 2) lung survival during perfusion with human blood. Neither agent consistently prolonged median lung survival (FUT: 50 min. +/- 28 SEM; K76: 37 +/- 16), blocked thromboxane production, or prevented PVR elevation compared to experiments using unmodified human blood (survival 9 min. +/- 2). At the doses used, both agents prevented deposition of terminal complement complex (TCC) in the lung. This finding demonstrates that the various phenomena associated with hyperacute lung rejection (thromboxane release, PVR elevation, capillary leak, and intraalveolar hemorrhage) can all occur despite abrogation of membrane attack complex formation. We can not exclude a contribution by drug toxicity or complement damage (mediated by C3a or other complement pathway components proximal to TCC) to the observed lung injury. We conclude that, although both FUT and K76 inhibit deposition of TCC in the lung, at the dose tested neither drug is useful as a single agent to prolong survival in a pig-to-human lung xenograft model.

Animals↗
PubMed2004

Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants.

At present, acute vascular rejection (AVR) remains a primary obstacle inhibiting long-term graft survival in the pig-to-non-human primate transplant model. The present study was undertaken to determine whether repetitive injection of low dose Yunnan-cobra venom factor (Y-CVF), a potent complement inhibitor derived from the venom of Naja kaouthia can completely abrogate hemolytic complement activity and subsequently improve the results in a pig-to-rhesus monkey heterotopic heart transplant model. Nine adult rhesus monkeys received a heterotopic heart transplant from wild-type pigs and the recipients were allocated into two groups: group 1 (n = 4) received repetitive injection of low dose Y-CVF until the end of the study and group 2 (n = 5) did not receive Y-CVF. All recipients were treated with cyclosporine A (CsA), cyclophosphamide (CyP) and steroids. Repetitive Y-CVF treatment led to very dramatic fall in CH50 and serum C3 levels (CH50 < 3 units/C3 remained undetectable throughout the experiment) and successfully prevented hyperacute rejection (HAR), while three of five animals in group 2 underwent HAR. However, the continuous suppression of circulating complement did not prevent AVR and the grafts in group 1 survived from 8 to 13 days. Despite undetectable C3 in circulating blood, C3 deposition was present in these grafts. The venular thrombosis was the predominant histopathologic feature of AVR. We conclude that repetitive injection of low dose Y-CVF can be used to continuously suppress circulating complement in a very potent manner and successfully prevent HAR. However, this therapy did not inhibit complement deposition in the graft and failed to prevent AVR. These data suggest that using alternative pig donors [i.e. human decay accelerating factor (hDAF)-transgenic] in combination with the systemic use of complement inhibitors may be necessary to further control complement activation and improve survival in pig-to-non-human primate xenotransplant model.

Animals↗
PubMed2005

The effect of soluble complement receptor type 1 on acute humoral xenograft rejection in hDAF-transgenic pig-to-primate life-supporting kidney xenografts.

BACKGROUND: In pig-to-nonhuman primate solid organ xenotransplantation using organs from donors transgenic for human decay-accelerating factor (hDAF), the main type of rejection is antibody-mediated (acute humoral xenograft rejection, AHXR). This occurs despite the complement-regulatory function of the transgene, neutralization of natural antibodies to Galalpha1-3Gal (Gal) using soluble glycoconjugates, and chronic immunosuppression. As complement components play a major role in graft destruction after antibody binding, we evaluated the efficacy of chronic complement inhibition by soluble complement receptor type 1 (TP10). METHODS: Life-supporting hDAF-transgenic kidney transplantation was performed in cynomolgus monkeys, using cyclophosphamide induction, and maintenance immunosuppression with cyclosporin A, mycophenolate sodium, and tapering steroids. Rejection was treated with bolus steroid injections: if not successful animals were terminated. Three groups were studied: in group 1 (n=4) GAS914 (a soluble glycoconjugate comprising Gal on a poly-L-lysine backbone) was added before and after transplantation; group 2 (n=2) received GAS914 as in group 1 and in addition TP10 before and after transplantation; in group 3 (n=4) GAS914 was only given before transplantation and TP10 as in group 2. Monitoring included the regular assessment of anti-porcine antibodies, complement activity (soluble C5b-9), therapeutic drug monitoring, and graft histology. RESULTS: Survival in group 1 was 6, 12, 31 and 37 days, respectively, and in all four cases graft histology showed AHXR. The two animals in groups 2 survived 3 and 15 days, respectively, and similarly showed AHXR in graft histology. In group 3 two animals showed AHXR (10 and 37 days survival, respectively), and two others did not show AHXR (20 and 32 days survival, respectively). The diagnosis AHXR included the deposition of complement activation products in the graft, which were present at lower intensity in animals treated with TP10. In all animals GAS914 effectively neutralized circulating anti-Gal antibody. Antibodies were detectable in the circulation of all animals using porcine erythrocytes in a hemolytic assay, although at lower levels than before transplantation. Soluble C5b-9 was not detectable in the circulation of animals receiving TP10, and circulating TP10 concentrations in these animals were in a presumed pharmacologically active range. CONCLUSIONS: The inclusion of TP10 in the immunosuppressive protocol does not clearly lead to improved xenograft survival. Despite effective neutralization of anti-Gal antibodies and effective inhibition of systemic complement activity, AHXR was apparent in four of six animals under chronic TP10 treatment, including deposits of complement activation products in the graft. Apparently, effective systemic complement inhibition by TP10 in combination with local complement regulation by the hDAF transgene product does not necessarily result in effective inhibition of complement activation at locations in the xenograft upon binding of anti-porcine antibodies to the grafted endothelium.

Acute Disease↗
PubMed1978

Anti-fab' antibodies in human sera. II. A study of their possible association with C-reactive protein, rheumatoid and anticomplementary factors.

The present study was undertaken to determine whether a relationship could be found between Fab' antibodies and the occurrence of C-reactive protein, rheumatoid and anticomplementary factors in the serum of patients with malignancies and other illnesses. The findings argue against the possibility that Fab' antibody activity is associated with a single disease entity. The very frequent occurrence of Fab' antibodies in hospital patients as opposed to healthy blood donors implies that their function is probably indirectly related to other immunological events. There is evidence to suggest that Fab' antibodies may serve as a mechanism for clearing immune complexes.

Antibodies, Anti-Idiotypic↗
PubMed1982

Antibody spectrum and anticomplementary activity of a plasmin-treated human immunoglobulin preparation.

A commercial plasmin-treated human immunoglobulin was studied for its antibody spectrum and anticomplementary activity. Except for a decrease in anti-vaccinia antibody titers in two of three paired samples collected before and after plasmin treatment, there was practically no fall in titers of diphtheria antitoxin and of antibodies to measles, rubella and mumps viruses. Among the three major fractions isolated from the preparation, the plasmin-resistant 7S IgG fraction showed the highest anticomplementary activity when tested by our routine method described in the "Japanese Minimum Requirements'. The Fab fraction showed moderate anticomplementary activity which was thought to be due to the selective consumption of C3. On the contrary, the Fc fraction was not found to be anticomplementary in our test method. In some of the above-mentioned features, the preparation seems to be different from the domestic product formerly studied by ourselves.

Antibodies↗
PubMed1998

Complement and biocompatibility.

Blood contact with foreign surfaces induces a certain degree of activation of the defence systems including complement. Recent data using complement specific inhibitors have shown that complement is not only associated with, but in fact contributes to the whole body inflammatory reaction seen as a complication of cardiopulmonary bypass (artificial surfaces) and is responsible for the hyperacute rejection of xenografts (foreign endothelium). Complement activation products, particularly the terminal SC5b-9 complex (TCC), is a sensitive indicator of bioincompatibility. Modifications of the artificial surfaces by coating with heparin improves both coagulation and complement compatibility. The use of specific complement inhibitors in general improves biocompatibility both of artificial materials and foreign endothelium.

Animals↗
PubMed1976

The role of the physical state of lipopolysaccharides in the interaction with complement. High molecular weight as prerequisite for the expression of anti-complementary activity.

Lipopolysaccharides interact with complement only when they are present in a state of high aggregation with a high apparent molecular weight. Lipopolysaccharides in uniform salt forms prepared by electrodialysis and neutralization with different bases exhibited distinct differences in their anticomplementary activity which correlated with differences in their sedimentation coefficients. Conversion of smooth (S) form lipopolysaccharides into the low-molecular-weight triethylamine form completely abolished their anti-complementary activity while conversion into the high-molecular-weight sodium form increased their activity. In contrast, a similar treatment of highly defective Re and Rd rough (R) form lipopolysaccharides had no effect on their ability to interact with complement. Both the triethylamine and sodium forms were strongly anti-complementary despite large differences in their molecular weight. This was found to be due to the property of R lipopolysaccharides to reaggregate into a large-molecular-weight form through absorption of Mg2+ and Ca2+ present in the guinea pig serum used as complement source. Defective lipopolysaccharides derived from the Ra and Rb classes showed only negligible anti-complementary activity which did not increase by conversion into salt forms with high molecular weight.

Amines↗
PubMed1982

Evidence for different requirements in physical state for the interaction of lipopolysaccharides with the classical and alternative pathways of complement.

The influence of the state of aggregation of lipopolysaccharides upon their ability to interact with serum complement via either the classical or alternative pathway was studied. The anticomplement properties of two chromatographically distinct fractions of a phenol-extracted lipopolysaccharide isolated from Serratia marcescens were assessed by means of the standard sheep erythrocyte hemolytic assay and an alternative pathway-selective kinetic assay using rabbit erythrocytes. Both the high molecular weight PI fraction and the lower molecular weight PII fraction exerted anti-complement activity as determined in the sheep erythrocyte assay. Conversion of fractions PI and PII to their more soluble triethylamine salt forms resulted in a decrease in sedimentation coefficients and a corresponding loss of anticomplement activity. Further, the anticomplement activity of fractions PI and PII in the sheep erythrocyte assay was inhibited by polymyxin B, indicating a role for the lipid A region. Unlike the PII fraction, only the PI fraction can activate serum complement via the alternative pathway. This activity is not inhibited by polymyxin B, indicating that the response is not lipid A-mediated. Significantly, solubilization of the PI fraction with triethylamine had no effect on its ability to activate the alternative pathway. These studies clearly demonstrate that the interaction between lipopolysaccharides and serum complement is influenced by the state of lipopolysaccharide aggregation. However, this appears to be the case for lipopolysaccharide activation of the classical pathway but not of the alternative pathway.

Adult↗
PubMed1991

Eicosanoid-mediated increase in glucose and lactate output as well as decrease and redistribution of flow by complement-activated rat serum in perfused rat liver.

Rat serum, in which the complement system had been activated by incubation with zymosan, increased the glucose and lactate output, and reduced and redistributed the flow in isolated perfused rat liver clearly more than the control serum. Heat inactivation of the rat serum prior to zymosan incubation abolished this difference. Metabolic and hemodynamic alterations caused by the activated serum were dose dependent. They were almost completely inhibited by the cyclooxygenase inhibitor indomethacin and by the thromboxane antagonist 4-[2-(4-chlorobenzesulfonamide)-ethyl]-benzene-acetic acid (BM 13505), but clearly less efficiently by the 5'-lipoxygenase inhibitor nordihydroguaiaretic acid and the leukotriene antagonist N-(3-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-propoxy]-4-chlorine-6-meth yl- phenyl)-1H-tetrazole-5-carboxamide sodium salt (CGP 35949 B). Control serum and to a much larger extent complement-activated serum, caused an overflow of thromboxane B2 and prostaglandin F2 alpha into the hepatic vein. It is concluded that the activated complement system of rat serum can influence liver metabolism and hemodynamics via release from nonparenchymal liver cells of thromboxane and prostaglandins, the latter of which can in turn act on the parenchymal cells.

Animals↗
PubMed1994

Prolongation of discordant renal xenograft survival by depletion of complement. Comparative effects of systemically administered cobra venom factor and soluble complement receptor type 1 in a guinea-pig to rat model.

There is an increasing body of evidence to suggest that inhibition of complement activation may be a valuable approach to avert hyperacute rejection. In our study, the guinea-pig to rat discordant kidney xenograft model was adapted for the investigation of renal transplant function and an attempt was made to delay the hyperacute rejection using systemically administered cobra venom factor (CVF) and soluble complement receptor type 1 (sCR1). The saline-treated control recipients experienced a rapid transplant rejection with a xenograft survival averaging 10.5 +/- 2.1 min. Administration of a single 60 U/kg i.v. bolus of CVF significantly prolonged renal graft survival to 20.4 +/- 2.5 h, and by a single bolus of sCR1 (50 mg/kg) a prolongation of graft survival to 18.8 +/- 2.3 h was achieved. The grafts functioned only over periods of 2.5 +/- 0.3 and 2.3 +/- 0.2 h, respectively. No complications of sCR1 were noted. We concluded that complement inhibition by sCR1 may be an important component in the therapeutic approach aiming at the prevention of hyperacute rejection in human organ transplantation.

Animals↗
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↗
PubMedDate not supplied

Evaluation of commercial antiglobulin sera over a two-year period. Part I. Anti-beta 1A, anti-alpha 2D, and anti-beta 1E levels.

Antiglobulin sera from nine different manufacturers have been tested, over a two-year period, for their ability to detect the complement components beta 1A, alpha 2D, and beta 1E. The results demontrate considerable variation in the abilities of sera from different manufacturers to detect these components and indicate that not all sera on the market are suitable reagents for diagnostic use and compatibility tests. The results also show that there is considerable variation between different lots of serum from some of the manufacturers. In general, the anti-complement levels of these reagents have increased during the two-year period of study but not all companies produce suitable reagents for routine use.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Anticomplementary activity in human semen and its possible importance in reproduction.

We demonstrated anticomplementary activity on once-washed human sperm, and in normal and vasectomized seminal plasmas. It was demonstrated to be a normal component of human semen. The origin of the activity is proposed to be the seminal plasma with sperm adsorption of activity. The properties of the seminal anticomplementary factor were characterized further, and the molecular size was shown to be less than 3500 daltons. Reduced anticomplementary activity was found to be associated significantly with abnormal semen profiles and infertility in males. The activity in seminal plasma was shown to have no effect on complement-dependent sperm immobilizing antibodies in the serum of an infertile woman, implicating an effect on the post-C3 components of the complement pathway. The inhibition of complement-dependent haemolysis and the lack of inhibition of complement-dependent sperm immobilization by the anticomplementary factor are considered in the implications of the role of seminal anticomplementary activity in reproduction.

Complement Inactivator Proteins↗
PubMed1992

Comparison of antithrombin III, protein C and protein S levels in capillary and venous blood of newborn infants.

The plasma concentrations of antithrombin III, protein C and protein S in capillary and venous blood samples obtained simultaneously from 30 neonates were compared in order to determine the suitability of using capillary blood for estimation of these proteins with anticoagulant action. Our findings showed that while capillary and venous blood did not differ significantly in antithrombin III functional activity and protein C antigen levels, the capillary samples had significantly lower protein C functional activity and higher antithrombin III antigen level. Protein S antigen level was also significantly higher in the capillary samples although the difference was relatively small. The capillary and venous concentrations of the binding protein of protein S, C4b binding protein, were almost identical.

Antigens↗