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Results for “Complement C1 Inhibitor Protein”

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At least 649 records · Page 36Linked to original sources
PubMed1999

Sex-limited protein: in vitro and in vivo functions.

Mouse complement component C4 exists in two isoforms, C4 and a protein with expression restricted to male animals called sex-limited protein (Slp). Although Slp is about 95% homologous to C4, it is generally believed to be non-functional, at least in conventional haemolytic complement assays. In a previous study, however, we showed that Slp is haemolytically active in a C1-inhibitor (C1INH)-regulated, EDTA-resistant mouse complement activation pathway. To study other possible implications of this finding, we generated constitutively expressing Slp-transgenic mice. The transgene was crossed into otherwise Slp-deficient C57Bl/6J and NZB mice. Members of the third backcross generation of C57Bl/6J mice were tested for functional Slp and classical and alternative complement pathway activities (CH50 and AP50 levels, respectively). Slp-transgenic C57Bl/6J mice showed enhanced CH50, but normal AP50 levels when compared with non-transgenic littermates. To discover a possible protective role for Slp in spontaneous systemic lupus erythematosus (SLE) in NZBxNZW (NZBxW) mice, the third backcross generation of Slp-transgenic NZB mice was mated with NZW mice and the development of SLE in the female offspring was followed. In these introductory experiments, Slp-transgenic NZBxW animals presented with a significantly extended life span. Our results imply that Slp is a mouse complement component with functions which partially resemble some of those of human C4A.

Animals↗
PubMed1990

Hereditary angioedema: its diagnostic and management perspectives.

Although hereditary angioedema accounts for only a small fraction of all cases of angioedema, it is the most common genetically linked clinical disorder caused by the deficiency of a protein associated with complement activation. Attacks may be complicated by incapacitating cutaneous swelling, life-threatening upper airway impediment, and severe gastrointestinal colic. Recent physicochemical and genetic studies have contributed significantly to our understanding of the structure of the inhibitor protein. Measurement of serum C4 titer is an efficacious screening test. Normal levels during symptomatic periods rule out the diagnosis, whereas decreased levels warrant determination of C1 esterase inhibitor titer by immunoassay or functional assay. The functional assay is necessary to ascertain the genetic variant form. The importance of making the correct diagnosis cannot be overemphasized. It can avert potentially fatal consequences, such as upper airway obstruction and unnecessary abdominal surgery. The application of short-term preventive measures can avoid complications associated with trauma. Finally, abatement or elimination of symptoms in patients with incessant and disabling attacks can be attained by long-term therapy with currently available attenuated androgens.

Angioedema↗
PubMed1987

A sensitive specific hemolytic assay for proenzyme C1.

The traditional hemolytic assay of the functional activity of C1, the first component of the classical complement pathway, was modified to permit differentiation between proenzyme (unactivated) C1 and the activated state of the enzyme (C1). A two-step assay was developed to quantitate proenzyme C1. The C1 sample to be assayed was first preincubated with C1 inhibitor, a process that specifically inhibits the enzymatic activity of C1 without affecting the subsequent activation of proenzyme C1 by EAC4, a model immune complex. Since the rate of reaction between C1 inhibitor, a serum regulatory protein, and C1 is concentration-dependent, this step is performed at high C1 and C1 inhibitor concentrations. Subsequent dilutions of the sample prevents C1 inhibitor-mediated inactivation of the C1 that is activated during the C1 hemolytic assay. Thus, in the presence of C1 inhibitor, the level of C1 hemolytic activity specifically reflects the activity of proenzyme C1, while in the absence of C1 inhibitor, the hemolytic activity reflects the total activity of C1. Both the absolute and the relative amounts of the proenzyme (unactivated) and activated C1 can thereby be quantitated in most samples. Furthermore, a partially purified C1 inhibitor reagent, easily prepared from serum, was shown to function identically to the purified C1 inhibitor, obviating the need for a multistep isolation procedure for this protein. Using this simple yet sensitive assay to investigate the efficiency of reconstitution of C1 activity from the purified components C1q, C1r, and C1s, we also find evidence for temperature- and concentration-dependent reaction steps in the formation of functional C1.

Animals↗
PubMed1987

Inactivation of influenza B virus by normal guinea-pig serum.

Normal guinea-pig serum (GPS) lacking detectable antiviral antibody efficiently neutralized the infectivity of influenza B virus grown in chick embryos or MDCK cells. The inhibitor was heat-labile and sensitive to trypsin digestion. This beta-like inhibitor required Ca2+ and the complement components C1 and C4 for its activity. In contrast, GPS did not inactivate influenza A virus. Influenza B virus from which the neuraminidase activity of the spikes on the viral envelope had been eliminated by trypsin digestion was also inactivated to a level comparable to untreated virus. Complement component C1 alone bound directly to influenza B virus and inhibited its haemagglutinin activity. We suggest that the beta-like inhibitor in GPS is a component of the classical complement pathway which is triggered by the protein moiety of influenza B virus haemagglutinin, leading to virus neutralization.

Animals↗
PubMed1977

Further studies on the identification of the subcomponents of the first component of complement after affinity chromatography of human serum on IgG-sepharose.

Affinity chromatography of serum on IgG covalently linked to Sepharose results in the retention of the proteins of the first component of complement (C1). A fraction called pool II is eluted from this column with 0.025 M EDTA and has previously been shown to contain C1s and a novel protein believed to be part of the C1 complex and called C1t. C1r has now been located in pool II and these three proteins were purified by DEAE cellulose chromatography. C1r and C1s were recovered in the proenzyme form and their identity was established by SDS polyacrylamide gel electrophoresis before and after reduction and alkylation, and on the basis of their esterolytic activities toward different substrates. The properties of C1r from pool II are contrasted with those of the protein recovered from the pool III eluate of the affinity column and previously thought to be C1r.

Chromatography, Affinity↗
PubMed1985

Depletion of complement by light and porphyrin does not depend on sequential activation.

The mechanism of complement depletion from human serum fortified with porphyrin and irradiated with light has been reinvestigated, with the conclusion that it did not depend on the normal sequence of complement activation. Thus, disappearance of the activities of C3, C4, and C5 was not dependent on divalent cations. Purified C3-C7 were labile to porphyrin/light treatment in the absence of other components. The depletion of C4 was not prevented by potent inhibitors of C1 and, unlike the depletion of C4 seen in response to aggregated gamma globulin, was insensitive to change in temperature. Electrophoresis showed an alteration of C3 unlike that caused by cobra venom factor and that light/porphyrin treatment nonspecifically altered many serum proteins.

Complement Activation↗
PubMed1988

Expression of functional human C1 inhibitor in COS cells.

Full length human C1 inhibitor cDNA was cloned into a vector suitable for transient expression in COS-1 cells. Transfected COS cells secreted an immunoreactive protein of Mr approximately 110,000 that appeared to be functionally equivalent to the plasma-derived protein as established by the following criteria: 1) ability to form sodium dodecyl sulfate-stable complexes with C1s, factor XIIa, and kallikrein; 2) inhibition of C1s-mediated C4 consumption; and 3) susceptibility to inactivation by the nontarget proteinase elastase. Quantitation of secreted recombinant C1 inhibitor by radioimmunoassay indicated that 72 h after transfection the level was approximately 2.2 micrograms/ml. Treatment of transfected cells with tunicamycin resulted in secretion of a protein of Mr approximately 90,000 that was also capable of complex formation with C1s.

Animals↗
PubMed1993

C1-inhibitor gene nucleotide insertion causes type II hereditary angio-oedema.

The polymerase chain reaction and nucleotide sequence analysis have been used to characterise a three nucleotide insertion in the eighth exon of one allele of the C1-inhibitor gene between nucleotides 16749 and 16750 in a kindred with type II hereditary angio-oedema (HAE). The effect of the resulting C1-inhibitor amino acid sequence alteration is discussed. This represents the first report of a nucleotide insertion in the C1-inhibitor gene causing type II HAE.

Amino Acid Sequence↗
PubMed1985

Human plasma kallikrein and C1 inhibitor form a complex possessing an epitope that is not detectable on the parent molecules: demonstration using a monoclonal antibody.

The inactivation of human plasma kallikrein (EC 3.4.21.8) by the inhibitor of activated complement component 1 (C1 inhibitor) induces the formation of a 1:1 stoichiometric kallikrein-C1 inhibitor complex and a proteolytically modified form of C1 inhibitor. We have produced a monoclonal antibody that recognizes the kallikrein-C1 inhibitor complex as well as modified C1 inhibitor but fails to react with virgin C1 inhibitor or native plasma kallikrein. This observation constitutes an unequivocal demonstration that the reaction between plasma kallikrein and C1 inhibitor leads to the emergence of an epitope that is undetectable on the parent enzyme and inhibitor molecules.

Antibodies, Monoclonal↗
PubMed1972

Ontogeny of the human complement system: in vitro biosynthesis of individual complement components by fetal tissues.

The human fetal liver is capable of synthesizing the biologically active form of the second (C2) and fourth (C4) components of complement as early as 8 wk after conception, and the inhibitor of C1 (C1 INH) as early as 11 wk after conception. Biologically active C3 was produced in vitro by fetal liver obtained at 14 wk gestation. These conclusions were based on the observations that isolated fetal livers produced biologically active C2, C3, C4, and C1 INH, that this production was temperature dependent and reversibly inhibited by well-known inhibitors of protein synthesis, and that (14)C-labeled amino acids were incorporated into proteins immunochemically identical with these proteins. The data suggested that a large mononuclear cell was the cell type in the fetal liver that synthesized C2 and C4.

Amino Acids↗
PubMed2003

Acquired angioedema and Helicobacter pylori infection in a child.

UNLABELLED: We describe a 10-year-old boy with acquired Helicobacter pylori infection and simultaneous angioedema which is a rare but life-threatening condition. Our patient was hospitalised with generalised angioedema and severe circulatory shock due to extreme loss of fluids and proteins into interstitial tissues (weight gain 10 kg within 2 days, extreme haemoconcentration--haemoglobin 206 g/l, haematocrit 0.570, leucocytosis 18,300 /microl, high lactate 13.8 mmol/l) and simultaneous failure of the complement system (C3 <0.16 g/l, C4 <0.13 g/l, CH50 45 U/ml, i.e. 50% of normal value, C1 inhibitor 0.21 g/l at the lower limit). All possible known causes of angioedema were excluded (infection, allergy, auto-immune disease, NSAIDs, lymphoproliferative disease) except for the simultaneous H. pylori infection which was proven serologically and histologically. Eradication therapy led to a complete remission of the H. pylori infection. An absence of angioedema and the restoration of the complement system was later observed. To the best of our knowledge, no similar case report of a child has yet been published. CONCLUSION: Helicobacter pylori infection should be considered in the development of angioedema in childhood.

Angioedema↗