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Results for “Complement C1 Inhibitor Protein”

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At least 343 records · Page 19Linked to original sources
PubMed1998

Tissue plasminogen activator (tPA) antigen in plasma: correlation with different tPA/inhibitor complexes.

In many studies, tPA antigen has been a strong predictor of myocardial infarction. However, only a few percent of the total tPA antigen present in plasma samples taken at rest constitutes active tPA. The rest is enzymatically inactive and consists of a heterogeneous mixture of tPA in complex with inhibitors such as PAI-1, antiplasmin and C1 inhibitor. In the present study we developed specific two-site ELISA methods for determining the individual protease/inhibitor complexes constituting tPA antigen. We subsequently measured the concentrations of the different complexes in plasma samples taken from 30 healthy individuals. The results show that the concentration of the complex between tPA and PAI-1 in plasma correlated strongly with that of tPA antigen in plasma, as measured with a commercially available kit. Also the correlation between tPA/PAI-1 complex levels in plasma and the PAI-1 activity concentration was significant. However, no significant correlations were found between tPA antigen concentration and tPA/C1 inhibitor or tPA/antiplasmin concentrations in plasma.

Adult↗
PubMed2000

Apical and non-polarized secretion of serpins from MDCK cells.

Corticosteroid binding globulin, a member of the serpin family, was previously shown to be secreted mainly apically from MDCK cells in an N-glycan independent manner [Larsen et al. (1999) FEBS Lett. 451, 19-22]. Apart from N-glycosylation, serpins are not known to carry any other posttranslational modifications, suggesting the presence of a proteinaceous apical sorting signal. In the present study we have expressed four other members of the serpin family: alpha1-antitrypsin, C1 inhibitor, plasminogen activator inhibitor-1 and antithrombin in MDCK cells. Tight monolayers of transfected cells were grown on filters and the amounts of recombinantly expressed serpins in the apical and the basolateral media were determined. alpha1-Antitrypsin and C1 inhibitor were found mainly in the apical medium whereas plasminogen activator inhibitor-1 and antithrombin were found in roughly equal amounts in the apical and basolateral media. Control experiments showed that all four serpins are transported along the exocytotic pathway in an uncomplicated way that does not involve transcytosis or differences in stability on the two sides of the cells. We conclude that some members of the serpin family including corticosteroid binding globulin, alpha1-antitrypsin and C1 inhibitor are secreted mainly apically from MDCK cells whereas plasminogen activator inhibitor-1 and antithrombin are secreted in a non-polarized manner.

Amino Acid Sequence↗
PubMed2002

Regulation of the mannan-binding lectin pathway of complement on Neisseria gonorrhoeae by C1-inhibitor and alpha 2-macroglobulin.

We examined complement activation by Neisseria gonorrhoeae via the mannan-binding lectin (MBL) pathway in normal human serum. Maximal binding of MBL complexed with MBL-associated serine proteases (MASPs) to N. gonorrhoeae was achieved at a concentration of 0.3 microg/ml. Preopsonization with MBL-MASP at concentrations as low as 0.03 microg/ml resulted in approximately 60% killing of otherwise fully serum-resistant gonococci. However, MBL-depleted serum (MBLdS) reconstituted with MBL-MASP before incubation with organisms (postopsonization) failed to kill at a 100-fold higher concentration. Preopsonized organisms showed a 1.5-fold increase in C4, a 2.5-fold increase in C3b, and an approximately 25-fold increase in factor Bb binding; enhanced C3b and factor Bb binding was classical pathway dependent. Preopsonization of bacteria with a mixture of pure C1-inhibitor and/or alpha(2)-macroglobulin added together with MBL-MASP, all at physiologic concentrations before adding MBLdS, totally reversed killing in 10% reconstituted serum. Reconstitution of MBLdS with supraphysiologic (24 microg/ml) concentrations of MBL-MASP partially overcame the effects of inhibitors (57% killing in 10% reconstituted serum). We also examined the effect of sialylation of gonococcal lipooligosaccharide (LOS) on MBL function. Partial sialylation of LOS did not decrease MBL or C4 binding but did decrease C3b binding by 50% and resulted in 80% survival in 10% serum (lacking bacteria-specific Abs) even when sialylated organisms were preopsonized with MBL. Full sialylation of LOS abolished MBL, C4, and C3b binding, resulting in 100% survival. Our studies indicate that MBL does not participate in complement activation on N. gonorrhoeae in the presence of "complete" serum that contains C1-inhibitor and alpha(2)-macroglobulin.

Adult↗
PubMed1996

Complement regulatory protein expression by a human oligodendrocyte cell line: cytokine regulation and comparison with astrocytes.

Rat oligodendrocytes spontaneously activate complement (C) and lack the C inhibitor CD59. As a consequence, rat oligodendrocytes are susceptible to lysis by autologous C in vitro. Expression of C inhibitors on human oligodendrocytes in vitro and other human glia has yet to be well characterized. We have previously shown expression at the mRNA level of the membrane inhibitors CD59, decay-accelerating factor (DAF; CD55) and membrane cofactor protein (MCP; CD46) in human astrocytes. We here examine the expression of membrane and secreted C inhibitors by the oligodendrocyte cell line, HOG. HOG cells abundantly expressed CD59, assessed at protein and mRNA level, and expressed DAF and MCP, albeit at a lower level. Expression of all three inhibitors was enhanced by incubation with interferon-gamma or with phorbol ester (PMA). Complement receptor type 1 (CR1; CD35) was neither expressed constitutively nor induced by cytokines. HOG also constitutively secreted C1-inhibitor, S-protein and clusterin. Factor H was secreted only after stimulation with cytokines. C4b binding protein was expressed at a very low level and was detected only at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR). For comparison, astrocyte expression of CD59, DAF, MCP and CR1 was confirmed at the mRNA and protein levels. HOG did not activate C spontaneously, as judged by the lack of deposition of C fragments, and were not lysed by C even after inhibition of CD59 and DAF using specific monoclonal antibodies.

Astrocytes↗
PubMed1985

Application of molecular cloning to studies on the complement system.

The isolation of cDNA and, in certain cases, genomic clones has been reported for the following complement proteins: C1q, C2, C3, C4, C5, C9, and factor B, C4b-binding protein and C1-inhibitor. The availability of cloned DNA has allowed rapid advances to be made in the understanding of the structure (from the derived amino acid sequences), function, biosynthesis and genetics of these proteins. This is most strongly illustrated from recent studies on the C2, factor B and C4 genes, which code for the class III molecules of the major histocompatibility complex, especially as certain allelic forms of these genes may be associated with disease susceptibility.

Animals↗
PubMed1990

Human monocytes release plasma serine protease inhibitors in vitro.

The ability of human peripheral blood monocytes to secrete plasma serine protease inhibitors was studied. Monocytes from blood obtained from healthy young adult volunteers were cultured for up to 36 h with and without lipopolysaccharide from Escherichia coli. The concentrations of plasma serine protease inhibitors in monocyte culture supernatants were measured by using rocket immunoelectrophoresis. The study showed that human monocytes stimulated with lipopolysaccharide in vitro release antithrombin III, C1 esterase inhibitor, alpha 2-antiplasmin, and alpha 2-macroglobulin.

Adult↗
PubMed2006

Proteome analysis of myocardial tissue following ischemia and reperfusion--effects of complement inhibition.

Myocardial ischemia-reperfusion injury can be related to complement activation with generation of chemotactic mediators, release of cytokines, leukocyte accumulation, and subsequent severe tissue injury. In this regard, activation of transcription factors (i.e., NFkappaB) and de novo protein synthesis or inflammatory protein degradation seems to play an important role. In the present study, we analyzed the cardiac protein expression following myocardial ischemia (60 min) and reperfusion (180 min) in a rabbit model utilizing two-dimensional electrophoresis and nanoHPLC/ESI-MS/MS for biochemical protein identification. To achieve cardioprotective effects, we used a novel highly selective small molecule C1s inhibitor administered 5 min prior to reperfusion. The reduction of myocardial injury was observed as diminished plasma creatine kinase activity in C1s-INH-248-treated animals (65.2+/-3 vs. 38.5+/-3 U/g protein after 3 h of reperfusion, P<0.05). With proteome analysis we were able to detect 509+/-21 protein spots on the gels of the 3 groups. A pattern of 480 spots with identical positions was found on every gel of myocardial tissue of sham animals, vehicle and C1s-INH-248-treated animals. We analyzed 11 spots, which were identified by mass spectrometry: Superoxide dismutase, alpha-crystallin-chain-B, mitochondrial stress protein, Mn SOD, ATP synthase A chain heart isoform, creatine kinase, and troponin T. All of these proteins were significantly decreased in the vehicle group when we compared to sham-treated animals. Treatment with C1s-INH-248 preserved levels of these proteins. Thus, blocking the classical complement pathway with a highly specific and potent synthetic inhibitor of the activated C1 complex archives cardio-protection by altering and preserving different anti-inflammatory and cytoprotective cascades.

Amino Acid Sequence↗
PubMedDate not supplied

Quantification of hemostatic proteins and activation products in synovial fluids from arthritic joints prior to and after induction of chemical synoviorthesis.

Synovial fluids drawn from joints of patients suffering from rheumatoid arthritis were investigated for their concentrations of proteins and activation markers of the complement, coagulation and fibrinolytic systems. A broad spectrum of plasmatic inhibitors and other hemostatic proteins were detectable by immunologic assays. Compared to normal plasma concentration ranges, levels of alpha 2-antiplasmin, antithrombin III, heparin-cofactor II, factor H, alpha 2-macroglobulin, inter-alpha-trypsin inhibitor, fibrinogen and particularly high molecular weight kininogen were found to be decreased when corrected for total protein content. However, highly elevated levels of C-reactive protein, factor XIII, PMN-elastase, prothrombin fragment F1+2, thrombin-antithrombin III, plasmin-antiplasmin and terminal complement-complexes as well as C5a were determined. Eight and 24 hours after induction of chemical synoviorthesis, a general increase in most of the parameters was observed. Statistically significant alterations were found for C1-inhibitor, factor H, alpha 1-antitrypsin, inter-alpha-trypsin inhibitor, factor XIII, protein C, thrombin-antithrombin III complexes and C5a.

Arthritis, Rheumatoid↗
PubMed1975

Acute anaphylaxis associated with serum complement depletion.

A 45-year-old woman with rheumatoid arthritis developed anaphylaxis 6 min after receiving a subcutaneous injection of lidocaine, followed by an intra-articular injection of lidocaine mixed with methprednisolone acetate. One hour after the onset of anaphylaxis, serum complement component levels were markedly depressed and remained so far 18 hr. Circulating immune complexes and antibodies to lidocaine could not be demonstrated. Neither lidocaine nor methylprednisolone acetate activated the patient's complement system in vitro. Subsequently, total hemolytic activity (CH50) levels were variable, complement component protein concentrations of C1q, C1s, C4, C2, C3, C5, C6, C9, and Factor B were normal, but hemolytic activity of C4 and C2 was diminished. Serum C1 inhibitor concentrations were normal or slightly depressed. The patient has never had any symptoms suggestive of angiodema. It is postulated that the endogenous complement abnormality present in this patient may have contributed to the anaphylactic reaction.

Anaphylaxis↗
PubMed1997

Activation of the contact system by filtration of platelet concentrates with a negatively charged white cell-removal filter and measurement of venous blood bradykinin level in patients who received filtered platelets.

BACKGROUND: Several recent reports have described hypotensive transfusion reactions in patients receiving platelet concentrates (PCs) filtered through white cell-reduction filters. It is well known that a negatively charged surface activates the contact system, consisting of factor XII, prekallikrein, and high-molecular-weight kininogen. STUDY DESIGN AND METHODS: To clarify the mechanisms of these hypotensive reactions, the possibility that white cell-reduction filtration activates the contact system was examined. Venous blood plasma bradykinin levels were also measured in patients receiving PC transfusions through filters. RESULTS: None of the measured values were changed by filtration through a positively charged filter. However, filtration through a negatively charged filter resulted in a decrease in the amounts of prekallikrein and an increase in the amount of bradykinin generated, which indicated the activation of the contact system. The bradykinin level was inversely related to the activity of angiotensin-converting enzyme (ACE) in the PCs and was elevated by addition of an ACE inhibitor. Although the venous blood plasma bradykinin level did not change in two patients with a normal ACE activity during PC transfusion through the negatively charged filter, two patients who had decreased ACE activity, showed a significant increase in bradykinin during the transfusion. CONCLUSION: These results suggest that the generation of a large amount of bradykinin by filtration of PCs through a negatively charged filter might cause hypotensive reactions in patients with decreased ACE activity. The clinical significance of bradykinin generation requires further study.

Aged↗