Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C1 Inhibitor Protein”

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 199 records · Page 11Linked to original sources
PubMedDate not supplied

Heparin and derivatized heparin inhibit zymosan and cobra venom factor activation of complement in serum.

Heparin has been shown to inhibit activity of the alternative, classical and terminal pathways of complement by regulating C1, C1 inhibitor, C4 binding protein, C3b, factor H and S-protein. In vivo, heparin inhibits cobra venom factor activation of complement in a dose-related manner in guinea pigs. However, the ability of heparin and of modified heparin to inhibit complement activation in serum has not been examined systematically. The present study compared commercial heparin with a modified heparin that has reduced anticoagulant activity (N-desulfated, N-acetylated heparin) for ability to inhibit cobra venom factor and zymosan-induced complement activation in guinea pig and human serum. Both heparins inhibited cobra venom factor and zymosan-induced consumption of C3 activity in both human and guinea pig serum. In both serum types, commercial heparin was about twice as active as modified heparin on a weight basis for ability to inhibit cobra venom factor-induced complement activation. Both heparins also inhibited zymosan-induced complement activation in human serum. About four times more heparin was required to inhibit cobra venom factor-induced complement activation in guinea pig serum than in human serum while heparin was more than ten times more active in human serum than in guinea pig serum when zymosan was used as the activator of complement. This study suggests that heparin is considerably more effective in regulating complement activity in humans than in guinea pigs, an animal model in which heparin clearly has in vivo capacity to regulate complement activity. These observations represent an important step in the development of new clinically relevant oligosaccharide-derived pharmacologic agents to regulate complement activity.

Animals↗
PubMed1993

Effects of choline-esterase inhibitor in experimental acute pancreatitis in rats. Preliminary results.

Choline-esterase inhibitor (C1-INH), a regulatory alpha-glycoprotein, was administered at different dosages and intervals to rats with induced acute pancreatitis. When compared to controls, treated rats showed no significant differences in the severity of histopathological lesions, such as edema and single cell necrosis. On the other hand, both mortality and extent of massive necrosis were significantly affected by C1-INH administration regardless of the dosages.

Acute Disease↗
PubMed1999

[Hereditary angioedema. Diagnostic and treatment errors as systemic lupus erythematosus].

BACKGROUND: Symptoms of hereditary angioedema are intermittent edema of subcutaneous tissues, abdominal organs, upper airways, and brain. Because of spontaneous mutation, in 20% of patients a familial history is lacking. Serological hallmarks are diminished complement factor 4 and C1-esterase inhibitor. The heterogenicity of the clinical symptoms frequently leads to false or delayed diagnosis. CASE REPORT: We report on a 50-year-old male patient with intermittent joint swellings, abdominal complaints, pleural effusions, ascites and headaches with disturbances of consciousness since early adulthood. Diagnosis was systemic lupus erythematosus. Immunosuppressive therapy was ineffective over months. Careful re-evaluation of the patient's clinical history and further laboratory examinations led to the diagnosis of an hereditary angioedema. Anamnestic and laboratory exploration of family members disclosed four other cases. Two of them also were symptomatic for decades without adequate diagnosis. CONCLUSION: In case of intermittent swellings, abdominal complaints, laryngeal edema, pleural effusions or ascites, differential diagnosis should involve hereditary angioedema. With early diagnosis and adequate treatment, prognosis is good. Since ACE inhibitors can aggravate the disease they are contraindicated. Diagnosis, pathogenesis, and treatment are discussed by reviewing the literature.

Angioedema↗
PubMed2001

Hereditary angioedema first apparent in the ninth decade during treatment with ACE inhibitor.

BACKGROUND: Hereditary angioedema ordinarily manifests itself in childhood. The development of angioedema in this disease and as a side effect of angiotensin-converting enzyme inhibitor treatment is caused by similar mechanisms. METHODS: We report a case of female patient, diagnosed with hereditary angioedema at age 90, who experienced the first attack 8 years earlier during angiotensin-converting enzyme inhibitor use. CONCLUSIONS: This patient presented with her first episode of hereditary angioedema at the oldest age ever reported. A careful family history, especially for angioedema, should be taken in patients of all ages before initiating treatment with angiotensin-converting enzyme inhibitor.

Aged↗
PubMed2006

Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrate.

BACKGROUND: Up to seven in every 1000 patients experience angioedema from angiotensin-converting enzyme (ACE) inhibitors, even after many years of use. In 2003, every 20th Norwegian used an ACE inhibitor. CASE REPORT: A 61-year-old woman with chronic obstructive pulmonary disease and a past acute myocardial infarction had used 7.5 mg of ramipril daily for the past 7 years. She also used acetylsalicylic acid, simvastatin, theophylline and salmeterol. One night she woke up with edema of the tongue. On hospital arrival, 250 mg of hydrocortisone and 5 mg of dexchlorpheniramine were given intravenously (i.v.) and 0.3 mg of epinephrine was given subcutaneously (s.c.). The edema of the tongue progressed over the next 8 h and made the tongue protrude. Fiberscopy revealed glassy edema of the arytenoids. Inspiratory stridor was heard and the patient could not speak. She became increasingly uneasy and restless. Berinert complement 1 (C1) inhibitor concentrate (1500 units) was administered i.v. Over the following 20 min, stridor gradually subsided, the patient calmed and she was able to talk. DISCUSSION: ACE inhibitor-provoked angioedema shares many clinical features with hereditary angioedema (HAE), including a limited effect of steroids, antihistamines and epinephrine. HAE, caused by excess bradykinin formation as a result of C1 inhibitor deficiency, usually has its laryngeal edema effectively reversed by C1 inhibitor in less than 0.5 h. Although patients experiencing ACE inhibitor-provoked angioedema have normal C1 inhibitor values, as in our patient, excess bradykinin is probably important as ACE breaks down bradykinin. It is unknown why ACE inhibitor-provoked angioedema appears in some and sometimes after many years of use. CONCLUSION: We believe that C1 inhibitor was effective in reversing the ACE inhibitor-induced angioedema in our patient.

Airway Obstruction↗
PubMed2001

[C1-esterase inhibitor in ACE inhibitor-induced severe angioedema of the tongue].

Angio-oedema are often massive but temporary swellings of the soft tissue of the face or the throat, which can also affect other regions of the human body (e.g. the skin or internal organs). An oedema of the face and throat represents a life-threatening situation. Apart from the clinical condition of the patient and detailed knowledge of the medical history (incl. medical applications), the treatment should depend on the different pathogenesis. In this reported case, we describe the severe clinical development of an angio-oedema under a long-term treatment with an ACE-inhibitor, which in the end was only successfully treated with the application of a C1 inhibitor concentrate.

Airway Obstruction↗
PubMed1987

Regulation of the activation of C1 in serum.

C1 has been partially purified from serum and its ability to activate has been studied. The activation status of C1 was measured using a sensitive hemolytic assay which allowed the activation status of C1 in serum to be monitored. C1 did not activate in serum but would spontaneously activate when separated from certain other serum proteins, in particular, the C1-inhibitor protein. The activation of C1 was time and concn dependent, but addition of fully activated C1 did not affect either the rate or extent of activation. The activation of C1 could be inhibited reversibly by C1-inhibitor. This action of the C1-inhibitor was over and above its ability to regulate fully activated C1 by covalent bond formation with either the serine esterase of C1s or C1r. The results presented suggest that the C1-inhibitor plays a dual role in the regulation of C1 activation. The regulatory actions of C1-inhibitor would account for the presence of C1 in a zymogen form and for the episodic nature of complement consumption observed in individuals with genetic deficiencies of the C1-inhibitor protein.

Chromatography, Ion Exchange↗
PubMed1992

Generation of anaphylatoxin C3a in plasma and bronchoalveolar lavage fluid in trauma patients at risk for the adult respiratory distress syndrome.

OBJECTIVE: To determine the generation of anaphylatoxin C3a in plasma and bronchoalveolar lavage fluid in trauma patients at risk for the adult respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: ICU in a university hospital. PATIENTS: Severely traumatized patients at risk for the ARDS (n = 25). INTERVENTION: EDTA plasma samples and bronchoalveolar lavage fluid were obtained. MEASUREMENTS AND MAIN RESULTS: Complement proteins C3, C4, C5, and the inhibitors C1-inhibitor, Factor H, and Factor I were quantitated in EDTA-plasma samples obtained every 6 hrs during the first 48 hrs after ICU admission and every morning from days 4 to 14 after injury. In bronchoalveolar lavage fluid, the complement activation production of C3a-desArg was quantitated and the volume of epithelial lining fluid was calculated. All patients showed a decrease of the complement proteins C3, C4, C5 and of the inhibitors C1-inhibitor, Factor H, and Factor I during the first 24 hrs, indicating complement consumption. Patients developing ARDS (n = 11) showed significantly higher C3 concentrations and a higher C3a/C3 ratio in the first few hours after multitrauma. Follow-up bronchoalveolar lavages demonstrated highly increased amounts of C3a in epithelial lining fluid during the first 24 hrs, mainly in ARDS patients and, to a lesser degree, in non-ARDS patients. To determine the origin of C3a in bronchoalveolar lavages, the ratio of C3a in epithelial lining fluid and plasma was calculated. CONCLUSION: The C3a of epithelial lining fluid to plasma ratio was extremely high in patients developing ARDS, but even the non-ARDS group had a ratio greater than 1, indicating that a substantial local complement activation occurs in the lung.

Adult↗
PubMed1998

High-dose intravenous immunoglobulin treatment activates complement in vivo.

Several complement modulating effects of high-dose intravenous immunoglobulins (IVIG) have been proposed from in vitro studies and experimental animal models. However, the in vivo effects of IVIG on plasma complement in humans are yet not known. We have investigated the in vivo effects of IVIG on complement in seven women with unexplained recurrent spontaneous abortion who were without evidence of autoimmune disease. Samples were obtained before and after the very first infusion of IVIG. There was a marked increase in immunoglobulin G (IgG) from (median and range) 12.4 (9.4-15.9) to 26.8 (22.4-30.0) g/l but no change in immunoglobulin A (IgA) or immunoglobulin M (IgM). A significantly increased complement activation was demonstrated using neoepitope-specific enzyme immunoassays to the activation products C3bc (median increased from 9.8 to 31.2 AU/ml), Bb (0.66-1.66 g/ml), C5a (10.5-12.7 ng/ml), and TCC (0.81-2.19 AU/ml) (P = 0.015 for all). There were no changes in antigenic concentrations of individual complement components or regulators (C1q, C4, C3, C1-inhibitor, C4b-binding protein) and no decrease in complement haemolytic activity (classical and alternative CH50), which were all within the normal range. The classical pathway activation products C1rs/C1-inhibitor complexes, C4bc and C4d were elevated in all patients before IVIG treatment and did not change significantly during treatment. In conclusion, IVIG induced a significant activation of complement in vivo.

Abortion, Habitual↗
PubMed1995

Synthesis of complement proteins in amnion.

The amnion is a metabolically active tissue that has been identified as a site of synthesis of numerous products. We report that amnion tissue explants and amnion-derived epithelial cells synthesize and secrete six proteins of the complement system, C1r, C1s, C1 inhibitor, factor B, C3, and factor H. Synthesis of C2 was minimal and variable, and C5 was not detected. The six synthesized proteins had size and subunit composition characteristic of proteins synthesized in HEp2, a long term cell line derived from malignant epithelial cells. Constitutive and regulated synthesis of five of the six proteins was similar in amnion tissue and cells. However, synthesis of factor B was different in tissue and cells; constitutive synthesis was 12-fold higher in tissue than in cells, and interleukin-1 did not alter synthesis in tissue, but increased synthesis by 11.7-fold in cells. These results indicate that amnion may be a source of complement proteins present in the amnion fluid and may contribute to local host defense along with endometrial glandular epithelial cells, which synthesize C3. Furthermore, our results suggest that amnion tissue is stimulated in vivo to synthesize factor B and cannot respond to interleukin-1 with a further increase in the synthesis rate.

Adult↗
PubMed1993

Influence of C1-inhibitor on inflammation, edema and shock.

C1-Inhibitor (Berinert, C1 INH), a 104 kDa protein, inhibits complement components (C1 esterase) as well as enzymes of the contact phase of coagulation (Factor XII, Factor XI) and kallikrein, thus regulating kinin generation. C1 INH is used for the treatment of the hereditary angioneurotic edema. This paper will give a survey about the evidence in recent literature concerning the potential efficacy of the compound on other diseases associated with shock, capillary leakage and inflammation as well. In our own experiments we evaluated whether the compound could influence acute inflammatory reactions or the severe systemic inflammatory response syndrome (SIRS) as a consequence of an experimental septic shock. To prevent the sepsis-induced DIC we co-infused the thrombin inhibitors AT III or rec. hirudin in combination with C1 INH. Coinfusion of C1-inhibitor (50-200 U/kg x h) with either rec. hirudin or AT III significantly improved survival rate compared to thrombin inhibitor alone.

Angioedema↗
PubMed1979

Evidence for glomerular modulation of complement activation.

Using indirect immunofluorescence, three regulatory proteins of the complement system, C1-inhibitor (C1-INH), C3b inactivator (C3bINA) and beta 1H globulin have been detected in the glomeruli of patients with glomerulonephritis associated with complement activation. C1-INH and beta 1H were found frequently but C3bINA was rarely detected (only 14 biopsies). beta 1H globulin and C3b inactivator which modulate C3b activity were never found in the absence of C3, but C1-INH was sometimes found in the absence of C1s. The patterns for staining for C1s and C1-INH, C3 and beta 1H were almost identical suggesting that the regulatory proteins are binding to the proteins they regulate, as has been demonstrated in vitro. Thus, in tissues undergoing complement-mediated tissue damage, the extent of complement activation is controlled by the normal regulatory mechanisms.

Complement Activation↗
PubMed1993

[Concentration of acute phase proteins in serum of children with rheumatoid arthritis].

An attempts was made at evaluation of the changes of acute phase proteins-seromucoid (BRS), alpha 1-acid glycoprotein (alpha 1-AGP), alpha 1-antitrypsin (alpha 1-AT), haptoglobin (Hp), C3 protein of complement system (C3), C1 esterase inhibitor (C1-INH), and transferrin (Tf) in the serum of children with rheumatoid arthritis. The patients were divided into clinical and age groups. The studies carried out have shown in ill children increase of BRS, alpha 1-AGP, alpha 1-AT, Hp, and C1-INH levels, During remission increased levels of alpha 1-AGP and Hp persisted. In the studied clinical groups a positive correlation was found between the intensity of changes of the studied indices and the degree of disease activity. In the age groups greater increase of the levels of the studied acute phase proteins was found in the group of preschool children and the group of puberty spurt. The obtained results suggest that the determination of acute phase proteins may be useful in laboratory investigation of children with rheumatoid arthritis.

Acute-Phase Proteins↗
PubMed2004

Mining biomarkers in human sera using proteomic tools.

One of the major difficulties in mining low abundance biomarkers from serum or plasma is due to the fact that a small number of proteins such as albumin, alpha2-macroglobulin, transferrin, and immunoglobulins, may represent as much as 80% of the total serum protein. The large quantity of these proteins makes it difficult to identify low abundance proteins in serum using traditional 2-dimensional electrophoresis. We recently used a combination of multidimensional liquid chromatography and gel electrophoresis coupled to matrix-assisted laser desorption/ionization-quadrupole-time of flight and Ion Trap liquid chromatography-tandem mass spectrometry to identify protein markers in sera of Alzheimer's disease (AD), insulin resistance/type-2 diabetes (IR/D2), and congestive heart failure (CHF) patients. We identified 8 proteins that exhibit higher levels in control sera and 36 proteins that exhibit higher levels in disease sera. For example, haptoglobin and hemoglobin are elevated in sera of AD, IR/D2, and CHF patients. The levels of several other proteins including fibrinogen and its fragments, alpha 2-macroglobulin, transthyretin, pro-platelet basic protein, protease inhibitors clade A and C, as well as proteins involved in the classical complement pathway such as complement C3, C4, and C1 inhibitor, were found to differ between IR/D2 and control sera. The sera levels of proteins, such as the 10 kDa subunit of vitronectin, alpha 1-acid glycoprotein, apolipoprotein B100, fragment of factor H, and histidine-rich glycoprotein were observed to be different between AD and controls. The differences observed in these biomarker candidates were confirmed by Western blot and the enzyme-linked immunosorbent assay. The biological meaning of the proteomic changes in the disease states and the potential use of these changes as diagnostic tools or for therapeutic intervention will be discussed.

Biomarkers↗
PubMed1989

[Release of proteinase inhibitors as a vital reaction in the early post-traumatic interval].

In a pilot study paraffin-embedded sections of open skin wounds (stab and slash wounds, lacerations) were investigated to determine the presence of a vital reaction. Granulocytes were detected by naphthol AS-D chloroacetate esterase, the enzyme "lysozyme", and eight proteinase inhibitors by the indirect immunoperoxidase method. The tissue specimens were taken from consecutive autopsy material. The survival time could be determined in 14 cases (10-165 min) and was unknown in 12 other cases of sudden death due to injury of the major vessels or heart. The controls were cases with injuries inflicted after and cases of sudden death due to massive blunt trauma served death. In vital injuries, accumulations of proteinase inhibitors, particularly alpha-2-macroglobulin and alpha-1-antichymotrypsin, were demonstrable in the corium parallel to the wound surface. In comparison, the reaction of proteinase inhibitors that neutralize only enzymes participating in blood coagulation or complement activation (C1-esterase inhibitor and protein C) was absent or weak. Protein accumulation was observed only sporadically in cases of sudden death and never in cases with wounds inflicted after death. No relationship could be established between semiquantitatively estimated staining and survival time. Granulocytes and lysozyme were first observed in the corium after a survival time of more than 60 min.

Granulocytes↗
PubMed1995

Posttransfusion anaphylactic reactions in a patient with severe von Willebrand disease: role of complement and alloantibodies to von Willebrand factor.

Previous studies have suggested that activation of the complement system might be a major mechanism for posttransfusion non-immunoglobulin (Ig) E-mediated anaphylactic reactions, but its causative effect has not been clearly demonstrated in human models. Serial plasma samples were collected from a patient with severe von Willebrand disease, IgG alloantibodies against von Willebrand factor (vWF), and a history of posttransfusion anaphylaxis. During an 18-day period the patient was treated with factor VIII-vWF concentrate and with recombinant factor VIII. Complement system activation was assessed from plasma levels of C4a, C3a, cleavage products of complement factor B, soluble terminal complement complex, C1 inhibitor and C4-binding protein, and the contact phase of coagulation was assessed from plasma levels of activated factor XII and cleaved high-molecular-weight kininogen. Plasma levels of antibodies to vWF and complement-fixing IgG-vWF complexes were also evaluated. Symptoms of anaphylaxis and signs of complement activation were present only when IgG antibodies to vWF were measurable during replacement with factor VIII-vWF concentrate (days 1 and 6). IgE, IgA, and IgM antibodies to vWF were not detectable in plasma at any time. Replacement with recombinant factor VIII (days 7 to 18) secured hemostasis and did not elicit anaphylactic reactions, and complement parameters did not significantly change even when antibodies to vWF reached peak plasma levels. This prospective study of a natural clinical model indicates a cause-effect relationship between formation of IgG-vWF complexes and massive complement activation in posttransfusion non-IgE-mediated anaphylactic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Molecular cloning of human C1 inhibitor: sequence homologies with alpha 1-antitrypsin and other members of the serpins superfamily.

Genetic and acquired diseases in man show that the proteolytic activity of the complement component C1 is crucially regulated by C1 inhibitor (C1-INH), a plasma protein whose suspected relatedness to other serine proteinase inhibitors (serpins) contrasts with its atypically large size and high degree of glycosylation. Indeed we have found that the C1-INH polypeptide precursor synthesized in a cell-free system is a 64-kDa protein, hence it exceeds the length of the precursor forms of typical serpins. Seeking more conclusive sequence information and a probe for the structural locus, we isolated C1-INH cDNA clones from a library representing size-enriched human liver mRNA. Nucleotide sequence analysis of a clone covering the carboxyterminal half of C1-INH conclusively documents the relatedness of this protein with the serpins, and reveals 27% amino acid identity with alpha 1-antitrypsin.

Cloning, Molecular↗