Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C1”

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 73 records · Page 4Linked to original sources
PubMed1985

Antibody density on rat red cells determines the rate of activation of the complement component C1.

It is a common observation that there is variability in the rate of activation of C1, the first component of complement, when bound to immune complexes. The cause of this variation has been investigated with experiments designed to assess separately the effect of antibody, antigen and C1 density. Using 125I-labeled C1 and a rat monoclonal antibody specific for the class I antigen, it has been found that the rate of activation is primarily dependent on antibody density on the cell surface and not on antigen or C1 density. This finding supports the suggestion that direct contact between the C1r2C1s2 subcomponent of C1 and antibody may be required for potentiation of C1 activation.

Animals↗
PubMed1977

Purification from euglobulin of the first component (C1) of complement and its subcomponents by heparin-sepharose chromatography.

Most of the C1 material of euglobulin was adsorbed to heparin-Sepharose at an ionic strength of 0.265. After desorbtion at an ionic strength of 0.415 the C1 material was found to be purified six to seven-fold. Highly purified subcomponents C1q, C1r and C1s were recovered at DEAE-Sephadex chromatography from such purified C1 material after EDTA-treatment. Tests on isolated C1q, C1r and C1s disclosed in addition to the well known interaction between heparin and C1q an equally strong or even stronger interaction between heparin and C1s. Even C1r was adsorbed to heparin although by somewhat weaker ionic bonds.

Chromatography, DEAE-Cellulose↗
PubMed1988

The distortive mechanism for the activation of complement component C1 supported by studies with a monoclonal antibody against the "arms" of C1q.

A mouse monoclonal antibody (IgG1 isotype) against human C1q (MAb 130) is presented that activates C1 in serum through its antigen-binding sites at an optimal molar ratio of 3 MAbs:1 C1q. The antibody does not inhibit binding of C1q to IgG. Experiments with pepsin- and collagenase-digested C1q showed that MAb 130 binds to the fibril-like strands (arms) of C1q, close to the globular heads. Bivalency of MAb 130 was a requirement for C1-activation, but not for binding to C1q. Increasing the segmental flexibility of the intact antibody by reduction and alkylation destroyed its capacity to activate C1. A MAb against the globular heads of C1q completely inhibited C1-activation by aggregated IgG (AHG), but did not prevent activation by MAb 130. C1, reconstituted by adding C1q-stalks that lack the globular heads to C1q-depleted serum was not activated by AHG, whereas activation by MAb 130 was not affected. Activation of serum-C1 by AHG and MAb 130 was inhibited by addition of excess purified C1-inhibitor in a comparable and dose-dependent manner. Sucrose-gradient analysis indicated a predominance of stable complexes of a single C1q-molecule with three MAbs at the optimal activating ratio. When isolated and added to C1q-depleted serum, these complexes activated C1 efficiently. A mechanism for activation by MAb 130 is proposed that supports the "distortive" model of C1-activation.

Antibodies, Monoclonal↗
PubMed1984

Formation of EAC142 and EAC1423 with macrophage culture supernatant containing the secreted complement components C1 to C3.

Culture supernatants of thioglycollate-elicited guinea pig peritoneal macrophages contained hemolytic C1, C4, C2 and C3, whereas hemolytic C5, C6, C7, C8 or C9 were not detected. Activity of C1, C2 and C3 increased up to a 48 h culture period, whereas C4 activity already declined in 2 day old cultures. After secretion, the hemolytic activity of C1 was least stable in culture supernatant. Sensitized sheep erythrocytes (EA) when incubated with culture supernatant initiated activation and functional cooperation of secreted C1 to C3 as indicated by formation of EAC142 and EA1423 intermediates. Decay and regeneration with purified C2 was shown for EAC142 and deposition of C3 fragments on EAC1423 was demonstrated with anti-C3. On an average, supernatants of 2 day old macrophage cultures were most suitable for formation of EAC142 and EAC1423 . The rate of EAC142 and EAC1423 formation, and also of C2 and C3 inactivation, during incubation of EA with culture supernatant was slow; addition of purified C1 to culture supernatant, however, greatly enhanced the same reactions of EA with supernatant which indicated that C1 was the rate limiting factor. Local secretion of hemolytic C1, C4, C2 and C3 by macrophages may have an important role in antimicrobial defense mechanisms due to the well-known functional cooperation between macrophages and activated C3.

Animals↗
PubMed1983

Complement components, C1 activation and disease activity in SLE.

Laboratory parameters were studied in 8 systemic lupus erythematosus patients during periods of high and low disease activity, mainly as defined by clinical criteria. Renal manifestations were present in 6 patients 5 of which showed antibodies to native DNA. C-reactive protein was raised in 3 patients. Only 1 of these showed a superimposed bacterial infection. Markedly high concentrations of C1r-C1s-C1 inactivator cOmplexes (C1r-C1s-Cl IA) in the sera provided direct evidence of C1 activation independent of disease activity. During active disease. C1r-C1s-C1 IA were correlated with C1q binding immune complexes as measured by solid phase, but not by fluid phase assay. Immunochemical concentrations of C1q, C4 and C3 and functional C2 were decreased in active SLE, consistent with sequential activation of the classical pathway. Discrepancies were noted between functional and immunochemical assay for C2 but not for factor B. Although essentially within the normal range, the levels of C1s, C4 binding protein, C5 and properdin were lower during active than during inactive disease. The concentrations of the factors B, I and H did not suggest involvement of the alternative pathway. 1 exceptional patient showed low factor B, a relative decrease of factor I and the presence of Bb fragments in plasma during active SLE. Markedly high factor D values were found. This could partly be explained by reduced renal function.

Adolescent↗
PubMed1990

Hydrodynamic data show that C1- inhibitor of complement forms compact complexes with C1-r and C1-s.

The C1- inhibitor of the complement cascade forms stoichiometric complexes with C1-r and C1-s and controls the activation of first component C1 of complement. Literature sedimentation coefficients s degrees 20,w for the complexes formed between C1- inhibitor, C1-r and C1-s were analysed using frictional ratios and the hydrodynamic sphere approach. A head-and-tail two-domain model for C1- inhibitor was combined with cylindrical hydrodynamic models for the six-domain structures of C1-r and C1-s. The hydrodynamic data show that the heavily glycosylated N-terminal domain of C1- inhibitor is positioned close to the two complement 'short consensus repeat' domains found in the centre of C1-r and C1-s.

Complement Activation↗
PubMed1984

Activation of C1.

The first component of complement, C1, is a calcium-dependent complex of two loosely interacting subunits: C1q, responsible for the binding of activators to C1; C1r2-C1s2, which supports the autoactivation potential of C1, together with the proteolytic activity of activated C1- on its two substrates, C4 and C2. Isolated dimeric C1r2 is able to autoactivate through an intradimer cross-proteolysis; this capacity is lost when C1r2 is associated with two molecules of C1s inside the calcium-dependent C1r2-C1s2 subunit; this capacity is again observed in reconstituted C1. A model for reconstituted soluble C1 is proposed, based on electron microscopy, neutron diffraction, ultra-centrifugation, various biochemical findings, as well as functional properties of C1 or of its subcomponents. The flexible rod-like structure of C1r2-C1s2 is folded around two arms of C1q, with the catalytic domains of C1r and C1s inserted inside the cone defined by the C1q stalks. Activation of C1 which, in vivo, is controlled by C1 inhibitor, can be achieved by various activators, such as immune complexes; it appears to result from the suppression of a negative control and resides in a positive modulation of the intrinsic autocatalytic potential of C1r inside C1.

Amino Acid Sequence↗
PubMed1988

On the interaction of the first complement component C1 and its subunit C1q with solid-phase IgM immune complexes.

The interaction of C1 and C1q with solid-phase anti-dextran MOPC-104E IgM was studied. An enzyme-linked immunosorbent assay (ELISA) was used to detect bound C1q. The results revealed that immobilized IgM is converted to the functionally active 'staple' conformation by the specific polyvalent ligand dextran (B 1355/S). C1q is fixed to IgM dependent on the antigen concentration, and its binding might be explained by assuming a functional binding constant (K) of approximately 10(9) M-1. Molecules bound with a K in the range of 10(7) M-1 cannot be detected by this ELISA procedure. The fixation of C1q saturated with an excess of the C1r2S2-tetramer differs from that of free C1q. C1q incorporated in the C1 complex rapidly dissociates independently of the antigen concentration. Since the complement binding sites are located at definite positions on the IgM molecule because of its pentameric structure, it is suggested that the distinguishable association properties of C1 and C1q are brought about from the altered flexibility of the C1q molecule complexed with C1r2S2.

Antigen-Antibody Complex↗
PubMed1987

[A case report of hereditary angioedema and studies on the serum components of complement, C1-inactivator and proteinase inhibitors during edema attack].

Sixteen years old girl was admitted because of for the past ten years' frequent edema attack and abdominal pain. Laboratory examination revealed hypocomplementemia, marked depletion of the fourth component of complement and low level of C1-inactivator. Familial studies revealed that her mother was also hypocomplementemic and in low level of C1-inactivator. Serial studies performed on the alterlation of components of complement, C1-inactivator, alpha 1-antitrypsin, antithrombin III, and alpha 2-macroglobulin during edema attack. The fourth component of complement and C1-inactivator were markedly depleted in remission and attack. Remarkable depletion was found in antithrombin III and esterase inhibition activity of C1-inactivator during attack. In contrast, alpha 1-antitrypsin and alpha 2-macroglobulin did not change. The present study may explain that Hageman factor fragments, activated by C1s, promotes kinin generation via kalikrein activation. And the condition that complete functional deficiency of C1-inactivator was main role in this circuit. Fibrynolysis and late components of complement was less influence on edema attack.

Adolescent↗
PubMed1985

Complement-subcomponent-C1-inhibitor synthesis by human monocytes.

By using a radioimmunoassay, C1-inhibitor was found to accumulate in the supernatants of human monocyte cultures. The production of this protein was inhibited reversibly by cycloheximide. When C1-inhibitor synthesis was compared with C2 synthesis, it was found that C1-inhibitor synthesis continued, whereas synthesis of C2 appeared to cease after about 7 days in culture. Immunoprecipitation of supernatants of monocyte cultures that had been pulsed with [35S]methionine showed a specific band with an Mr of 105 000. Immunoprecipitates of the lysates revealed a band of Mr 83 000; this was thought to represent a partially or non-glycosylated precursor of C1-inhibitor. C1-inhibitor produced by the monocytes was shown, by using a haemolytic assay, to be functionally active. However, the functional activity of C1-inhibitor was reduced by only 44% in the presence of cycloheximide, whereas the concentration of this protein in cycloheximide-treated culture supernatants fell by more than 93%. This finding suggests that monocytes secrete a second molecule, which inhibits C1 activity but is distinct from classical C1-inhibitor.

Cells, Cultured↗
PubMed1987

Antibody-independent activation of C1. II. Evidence for two classes of nonimmune activators of the classical pathway of complement.

Nonimmune activation of the first component of complement (C1) by cardiolipin (CL) vesicles present specific features which were not demonstrated on immune complexes. CL vesicles which activate C1 in the presence of C1-inhibitor (C1-INH) were found to bind C1s in the absence of C1r, and to induce a specific C1r-independent cleavage of C1q-bound C1s. Therefore, several known natural nonimmune activators were analyzed by comparing their ability to activate C1 in the presence of C1-INH and to mediate a C1r-independent cleavage of C1s. Freshly isolated human heart mitochondria (HHM) activated C1 only in the absence of C1-INH. However, mitoplasts derived from HHM (HHMP) activated C1 regardless of the presence of C1-INH, and induced a specific cleavage of C1q-bound C1s. The same pattern was observed in the case of smooth E. coli and a semi-rough E. coli strain. DNA, known to activate C1 only in the absence of C1-INH, does not induce C1s cleavage in the absence of C1r. Thus, nonimmune activators can be classified into two distinct categories. "Strong" activators, such as CL vesicles, HHMP, or the semi-rough E. coli strain J5 can activate C1 in the presence of C1-INH. By using C1qs2 as a probe, they exhibit a specific, C1r-independent cleavage of C1s. C1s-binding to C1q is a critical factor for the activation process in this group. In the case of "weak" activators, such as E. coli smooth strains, DNA, or HHM, no C1s-binding to activator-bound C1q was detected, and C1r-independent C1s cleavage and C1 activation in the presence of C1-INH were not observed. As in the case of immune complexes, C1r activation appears to play a key role in the C1 activation by "weak" activators.

Calcium↗
PubMed1979

Complement components (C1, C2, C3, C4) in bronchial secretions after intranasal infection of guinea pigs with Mycoplasma pneumoniae: dissociation of unspecific and specific defense mechanisms.

Shortly after intranasal infection of guinea pigs with Mycoplasma pneumoniae, the titers of the complement components increased significantly in bronchial secretions by the folllowing amounts, compared with the titer of a control group: C1, about 2-fold; C2, 1.6-fold; C3, 17-fold; and C4, 942-fold. Histopathological signs of inflammation were not apparent at this time. At 2 weeks after infection, when the titers of complement components in the bronchial secretions were at the level of control values or lower, the serum antibody titer increased, and it reached the highest level at 6 weeks after infection. Therefore, one can distinguish two phases of reaction of the macroorganism to intranasal inoculation. The increase in complement components shortly after infection may represent an earlyunspecific defense mechanism of the host before the specific immune response becomes effective, since the complement system can be activated by M. pneumoniae via the classical as well as the alternative pathway in the absence of antibodies.

Administration, Intranasal↗
PubMed1984

Neutron scattering studies of subcomponent C1q of first component C1 of human complement and its association with subunit C1r2C1s2 within C1.

Neutron scattering studies are reported on subcomponent C1q of component C1 of human complement, and on C1, the complex of C1q with subunit C1r2C1s2. For C1q, the molecular weight was determined as 460,000. The radius of gyration at infinite contrast RC is 12.8 nm. The RC values for the proteolytically cleaved forms of C1q, namely the heads and the stalks, are 1.5 to 2 nm and 11 nm, respectively, and thus the axis-to-arm angle of C1q is estimated at 45 degrees. Neutron data for subunit C1r2C1s2 are published elsewhere. The neutron data on C1 lead to an RC value of 12.6 nm for proenzymic C1 and a molecular weight of 820,000. The wide-angle scattering curve of C1q exhibits a minimum at Q = 0.28 nm-1 and a maximum at 0.39 nm-1; on the addition of C1r2C1s2, this minimum disappears. The neutron data on C1 indicate that C1q and C1r2C1s2 have complexed with a large conformational change in one or both parts. No conformational changes can be detected on the activation of C1 by this method.

Complement Activating Enzymes↗
PubMed1977

Interactions between mycoplasma pneumoniae and the first components of complement.

Mycoplasma pneumoniae cells were rounded and killed by fresh guinea pig serum (GPS) which did not contain detectable amounts of antibody. The first component of complement (C1) was bound by M. pneumoniae in considerable amounts from both GPS and purified C1. The C1 bound by the cells was reacting with C4. Sequential addition of C1, C4, C2, and C-ethylenediaminetetraacetate to glass-grown M. pneumoniae cells resulted in rounding of a significant number of cells. M. orale and M. fermentans showed a reduced binding capacity for C1 as compared with M. pneumoniae. Both species were only slowly killed by fresh GPS, whereas M. hominis was as sensitive as M. pneumoniae. The results suggest an antibody-independent interaction between some components of the membrane surface of M. pneumoniae and C1, resulting in an activation of the complement system leading to the killing of the mycoplasma cells.

Animals↗
PubMed1978

The presence of active C1 (C-1) on peripheral human lymphocytes.

We have shown that the first component of complement C1 is present in an active form on the surface of washed human peripheral lymphocytes but not on platelets or erythrocytes. This active C1 (C-1) was detected by its ability to transfer to sensitized cells carrying C4, i.e., EAC4, forming EAC-1,4. Active C1 was also able to consume C4. Treatment of these lymphocytes with 0.02 M EDTA removed C-1. EDTA-treated lymphocytes were able to bind exogenous purified human C-1. Comparative studies with sentized erythrocytes (EA) and EDTA treated lymphocytes showed that although fewer molecules of exogenous C1 could bind to the EDTA-treated lymphocytes than to EA, the consumption of C4 by C-1 bound to lymphocytes was significantly higher than that observed with EAC-1. When lymphocytes obtained from 2 patients with chronic lymphocytic leukemia and hypocomplementemia were tested, the release of C1, the C4 consumption and the binding of C-1 to EDTA-treated cells were highly inefficient.

Blood Platelets↗