Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement Pathway, Classical”

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 253 records · Page 14Linked to original sources
PubMed1983

A simplified quantification method of complex-release activity using peroxidase as immune complex antigen.

The complement-mediated solubilization of precipitable immune complexes (complex-release activity) in serum specimens was determined by a simplified method using peroxidase as an immune complex antigen. The results correlated well with the hemolytic activity via the classical complement pathway and that via the alternative complement pathway. This simplified method proved to be reliable and useful.

Antigen-Antibody Complex↗
PubMed1992

Induction of contact sensitivity by cell-associated immunocomplexes requires activation of the early complement components.

Lymph node cells collected from CBA/J mice 4 days after painting the skin with picryl chloride behave like antigen presenting cells and induce contact sensitivity when injected into naive recipient mice. The immunizing capacity of these '4-day' cells is due to T cells which carry on their membrane hapten-IgM immunocomplexes. Incubation of the cells with complement from mouse strains that express high C4 serum levels (C4H), abolishes their immunizing capacity. This effect is related to the activation of the early components of the classical complement pathway, as supported by experiments using C3 and C4-depleted or C5 and C6-genetically deficient mouse sera. The detection of different amounts of C3b and C4b on the surface of 4-day T cells after incubation with C4L and C4H sera supports the possibility that membrane bound activated complement components could modify the immunizing capacity of these cells. Results herein reported suggest that membrane-bound C3b and C4b are not per se inhibitory but interfere with the residual complement activating capacity of 4-day T cells. The role of complement activation by 4-day T cells is pivotal as complement depletion of recipient mice by cobra venom factor (CVF) inhibits the immunizing capacity of untreated 4-day T cells, while 4-day T cells treated with complement in vitro and injected together with C4a anaphylatoxin are able to immunize recipient mice.

Animals↗
PubMed1990

[Complement activation by killed polyvalent bacterial vaccine on the pleurodesis].

Broncasma Berna (B.B.) prepared from killed polyvalent bacterial vaccine is used as a pleural irritant for pleurodesis on patients with spontaneous pneumothorax. The effects of B.B. on the complement system in vivo after injections into pleural spaces were investigated. Five patients with spontaneous pneumothorax underwent intrapleural injections of B.B. Increased body temperatures with positive C-reactive proteins and increased polymorphonuclear leukocyte counts in peripheral blood were observed in all patients. Serum levels of complement components (Clq, Cls, C4, C3 and B), hemolytic activity of complement (CH50) and plasma levels of C3a were gradually elevated after intrapleural injections of B.B. Analysis of pleural fluids from 4 patients showed that levels of C3a and C5a were increased compared with plasma levels, and an accumulation of polymorphonuclear leukocytes were observed. These findings suggest that intrapleural injections of B.B. activate the complement system and cause inflammatory reactions accompanied by an increase of C3a and C5a and an accumulation of polymorphonuclear leukocytes. Such inflammatory reactions might inversely induce the synthesis of complement components and promote the migration of polymorphonuclear leukocytes from bone marrow. The deposit of fibrin during these inflammatory processes might contribute to the development of pleurodesis. These inflammatory reactions might be mediated through the activation of the classical complement pathway by B.B.

Adult↗
PubMed1990

[Fatal pneumococcal meningitis in a 1-year-old child with homozygous C2 deficiency].

The 1-year old girl died of recurrent bacterial meningitis. Streptococcus pneumoniae was isolated from the cerebrospinal fluid. The analysis of the immune system revealed only a defect of the complement system. The following results were obtained: 1. No function of the classical complement pathway. 2. Reduced function of the alternative complement pathway. 3. No functional C2 activity. 4. No C2 protein. The parents had half normal C2 titers. HLA typing was only possible for the parents with the following results: A1, A32(w19), B18, DR2, DRw11(5) (father) and A3, A10, B18, B7, DR2 (mother). These data are compatible with a B18, DR2 haplotype of the child which is found in most cases of homozygous C2 deficiency. Our patient list another example for the high risk of recurrent severe infectious diseases in persons with a total complement defect.

Complement C2↗
PubMed1989

Murine membrane inhibitor of complement which accelerates decay of human C3 convertase.

A membrane protein of MW 60,000 was purified from mouse erythrocytes. This protein inhibits generation of mouse complement C3/C5 convertases on antibody-sensitized rabbit erythrocytes, in a haemolytic assay system using guinea-pig serum diluted in EDTA as the source of C3 to C9. This protein also has the capacity to accelerate the decay of human C3 convertase of the classical complement pathway. Antibody to this membrane protein also reacted with peripheral blood mononuclear cells and spleen cells, as observed by fluorescent flow cytometry analysis. Since the reactivity of these cells to the antibody was reduced by treatment with phosphatidyl inositol-specific phospholipase C (PIPLC), it is suggested that the protein is attached to the membrane via a glycophospholipid anchor. Based on these results, we conclude that this membrane protein is a murine homologue of human decay-accelerating factor (DAF).

Animals↗
PubMed1987

Deficiency of C2, the second complement component, in the family of a patient with SLE-like syndrome: the first case of hereditary C2 deficiency in Czechoslovakia.

A family with hereditary C2 deficiency was discovered in Czechoslovakia. The proband is a 47-year-old female with a SLE-like syndrome and zero activity of the classical complement pathway. Functional CH50, C1, C2, and C4 estimations for all family members revealed a homozygous C2 deficiency in both the proband and her elder sister, and several heterozygotic C2-deficient individuals. The defect segregates with haplo-type HLA A25, B18, DR2.

Adult↗
PubMed1979

Neonatal cellular and humoral immunity to group B streptococci.

The mechanisms of host resistance to group B streptococci have not been defined precisely. In the studies reported here we have assessed the contributions of both humoral and cellular factors in protection against strains of this group. With assays of specific opsonic activity based upon the production of polymorphonuclear leukocyte chemiluminescence and radiolabeled bacterial uptake, we have demonstrated that specific heat-stable antibody and the classic complement pathway are major factors in opsonization of these organisms. In the absence of specific antibody, fresh serum resulted in markedly reduced bacterial uptake indicating, at best, a minor role for the alternative complement pathway. Additional studies have indicated that strain-specific antiphagocytic factors as well as type-specific ones may play a role in the virulence of these organisms. Neonates who developed group B streptococcal sepsis usually lacked opsonic activity in their infecting strain. In addition, polymorphonuclear leukocytes from normal term and stressed neonates showed impaired metabolic activation as measured in the chemiluminescence assay following exposure to opsonized group B streptococci. These results suggest that neonates who develop group B streptococcal disease may have defects in both the humoral and cellular aspects of their acute inflammatory response which may contribute to the high mortality observed in this most fulminant of bacterial infections.

Antibody Formation↗
PubMed1983

Demonstration of beta 1H globulin in pemphigus.

beta 1H globulin is a plasma protein which regulates the biologic activities of the major fragment of the 3rd complement component, C3b. The role of beta 1H globulin in pemphigus was investigated using immunofluorescence in the present study. Lesional skin biopsies from patients with confirmed pemphigus demonstrated in-vivo deposition of beta 1H in addition to C3 in all of four biopsies. Eight serum samples containing C3 fixing intercellular antibodies were then tested for the capacity to fix beta 1H and other complement components. All eight pemphigus sera showed fixation of beta 1H to the intercellular areas of normal human skin. C1q and C4 fixation by pemphigus sera was also demonstrated in 7 of 8 sera, respectively. The experiment using C2-deficient serum indicated that the fixation of beta 1H by intercellular antibodies requires the activation of the classical complement pathway. These data suggested that beta 1H, a co-factor of C3b inactivator, plays a role in the in-vivo regulation of complement activity and supplies additional evidence for the participation of complement system in the pathogenesis of pemphigus.

Antibody Specificity↗
PubMed1980

Depletion of total hemolytic complement in sera from hamsters bearing herpes simplex type 2-induced tumors.

Total hemolytic complement (CH50) levels were compared in sera from normal hamsters and hamsters bearing tumors derived from herpes simplex virus type 2-transformed cells CH50 in normal sera ranged from 160 to 212 while CH50 in tumor bearer sera ranged from 82 to 146. Preincubation of tumor bearer sera with cell surface proteins (CSP) from homologous herpes simplex virus type 2-derived tumor cells resulted in a 66% depletion of CH50 whereas preincubation with heterologous herpes simplex virus type 1-derived tumor CSP resulted in a decrease of 26%. The depletion of CH50 appeared to occur via the classic complement pathway. Similar results were seen using CSP from herpes simplex virus-infected cells although overall depletion of CH50 was considerably less than that seen using tumor cell material. Using the complement subcomponent 1q(C1q)-binding test, tumor bearer sera and tumor bearer sera preincubated with homologous CSP were shown to contain increased levels of immune complexes not present in normal serum. These results indicate that the observed depletion of complement activity in sera from tumor-bearing hamsters could be the result of complement pathway activation by antigen-antibody complexes.

Animals↗
PubMed1986

Serotherapy of primary rat mammary carcinoma: inhibition by ethylenedinitrilotetraacetic acid but not by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid.

We reported inhibition of growth of primary rat mammary carcinomas after infusions of tumor-bearer plasma absorbed with Protein A-Sepharose or inactivated CNBr Sepharose. Absorbed plasmas were depleted of the third component of complement (C3) (other complement components defined similarly) and C5 but not C1, C4, or C2. These results suggested that activation of the alternative pathway of complement might be involved in the observed antitumor effects. To test this concept sera were treated with ethylenedinitrilotetraacetic acid or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid before absorption with Protein A-Sepharose. Ethylenedinitrilotetraacetic acid, by chelating calcium and magnesium, prevents activation of both the alternative and classical complement pathways. [Ethylenebis(oxyethylenenitrilo)]tetraacetic acid, by chelating calcium but not magnesium, permits activation of the alternative pathway but inhibits activation of the classical complement pathway. Sera in the presence or absence of chelating agent were absorbed with Protein A-Sepharose twice at room temperature. After absorption calcium was added to the sera. Rats were treated by i.v. injection of sera twice a week for 2 weeks. Measurements of tumor size were made weekly for 5-7 weeks and then tumor weight was determined. Groups were compared both for size of index and total tumors. The results can be summarized as follows: tumor-bearer sera before absorption did not inhibit the growth of rat primary mammary carcinomas; tumor-bearer sera after absorption with Protein A-Sepharose showed significant consumption of C3 and did inhibit tumor growth; tumor-bearer sera absorbed in the presence of ethylenedinitrilotetraacetic acid did not show a decrease in C3 functional activity and did not inhibit tumor growth; tumor-bearer sera absorbed in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid did show a decrease in C3 functional activity and did inhibit tumor growth; sera from normal adult female rats after absorption with Protein A-Sepharose did inhibit tumor growth. The results are consistent with a role for the alternative pathway of complement in the inhibition of growth of rat primary mammary carcinomas observed after treatment with absorbed sera.

Animals↗
PubMed1979

Requirements of immunoglobulin and the classical and alternative complement pathways for phagocytosis and intracellular killing of multiple strains of Gram-negative aerobic bacilli.

The requirements for immunoglobulin and the alternative and classical complement pathways for phagocytosis and intracellular killing of clinical isolates of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Serratia marcescens by normal human polymorphonuclear leukocytes were determined. Human sera deficient in immunoglobulin or classical pathway activity, or both, were compared for their ability to promote phagocytosis os and killing of 13 bacterial strains by the polymorphonuclear leukocytes. Seven of the thirteen microorganisms required immunoglobulin for phagocytosis and killing and utilized only the classical complement pathway. Three required immunoglobulin and utilized both the classical and alternative pathways. The other three microorganisms required minimal immunoglobulin and utilized the alternative or classical pathway, or both. None of the microorganisms utilized the alternative pathway in immunoglobulin-deficient sera or could be forced to utilize this pathway in sera deficient in both immunoglobulin and classical pathway activity. These results demonstrated a heterogeneity in the requirements for immunoglobulin and the alternative and classical complement pathways for phagocytosis and intracellular killing by polymorphonuclear leukocytes among various genera of gram-negative aerobic bacilli, as well as among strains of the same species. In addition, the results suggested that a mechanism of classical pathway activation dependent upon minimal immunoglobulin participates in phagocytosis and intracellular killing of certain gram-negative aerobic bacilli.

Complement Activation↗
PubMed1990

In vitro phosphorylation of human complement factor C3 by protein kinase A and protein kinase C. Effects on the classical and alternative pathways.

Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2(+)-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Km for C3 was 2.6 microM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that phosphorylation of C3 in the C3a portion of the alpha-chain inhibited both the classical and alternative complement activation pathways on an approximately stoichiometric basis.

Amino Acids↗
PubMedDate not supplied

Role of complement in host resistance against members of the Bacteroidaceae.

Considerable evidence has been reported in recent years suggesting that complement plays an important role in host resistance against members of the Bacteroidaceae. Most of the investigations in this area have focused on the genus Bacteroides because of its clinical importance. Various species of Bacteroides have been shown to activate the complement system in vitro via the classical and alternative pathways. Complement activation results in the generation of chemotactic factors that mobilize polymorphonuclear leukocytes to sites of infection. Activated complement also facilitates bacteriolysis and opsonophagocytic killing by polymorphonuclear leukocytes and macrophages. Strains possessing dense fibrillar polysaccharide capsules are resistant to both of these defense mechanisms. The putative importance of complement-dependent bacteriolysis and opsonophagocytic killing in resistance against Bacteroides infections in vivo requires confirmation. In addition, the role of complement in synergistic interactions between Bacteroides and facultative bacteria remains to be elucidated.

Antibodies, Bacterial↗
PubMed1986

The pathogenesis of hyaline arteriolosclerosis.

Although hyaline arteriolosclerosis is very common and has been of interest to pathologists for well over 100 years, its pathogenesis has never been determined. This study demonstrates that iC3b bound via an ester linkage to hydroxyl groups on the repeating disaccharide units of hyaluronic acid is a major component of arteriolar hyaline. The deposition of iC3b within the walls of arterioles appears to be due to slow spontaneous activation of the alternative complement pathway and random binding of metastable C3b to proximate hyaluronic acid within the arteriolar wall. Since hyaluronic acid does not activate the alternative complement pathway, bound C3b is rapidly inactivated by factors I and H to iC3b, which, along with factor H, remains bound to hyaluronic acid. The hyaline in some hyalinized arterioles also contains IgM and early and late classical complement pathway components. Indirect evidence suggests that the IgM represents immunoconglutinin, an autoantibody to neoantigens on iC3b and that their interaction results in activation of the classical complement pathway. The gradual accumulation of iC3b, factor H, and, at times, IgM and classical complement pathway components within the walls of arterioles is considered to be a physiologic consequence of aging and probably cannot be prevented, because interruption of the initial binding of metastable C3b to hyaluronic acid would require abrogation of the critically important functions of the alternative complement pathway.

Adolescent↗
PubMed1991

The role of immunoglobulin and complement in enhancing the respiratory burst of neutrophils against Trichomonas vaginalis.

Human neutrophils, alone, did not kill Trichomonas vaginalis. More than 90% of T. vaginalis (10(5)/ml) survived in the presence of 10% normal human serum (NHS) while 90% of these organisms were killed in the presence of a combination of neutrophils (10(6)/ml) and 10% NHS. Mechanisms responsible for this serum-mediated neutrophil killing of T. vaginalis were demonstrated through a process of lucigenin-amplified neutrophil chemiluminescence. As evidenced by indirect immunofluorescence, NHS showed specific immunoglobulin G (IgG) titre of 1:8 for T. vaginalis. Purified IgG, at 1.6 mg/ml, showed no direct opsonizing or lytic effect on this organism. Formalin-fixed trichomonads opsonized by C2 deficient human serum promote 4 times more neutrophil chemiluminescence than those opsonized by Factor B deficient human serum. With the addition of purified IgG (5 mg/ml) neutrophil chemiluminescence was increased by 4 times and further improved trichomonal killing by neutrophils (from 5 +/- 4% to 78 +/- 16%) via activation of the classical complement pathway, but did not alter that due to activation of the alternative complement pathway. These studies indicate that both an IgG-enhanced classical complement pathway activation and an antibody-independent alternative complement pathway activation provide opsonin (C3) for T. vaginalis to facilitate the neutrophil killing mechanism.

Adult↗
PubMed1984

Serum sensitivity of Neisseria gonorrhoeae: the role of lipopolysaccharide.

A lipopolysaccharide (LPS) mutant (FA5100) of a serum-resistant strain of Neisseria gonorrhoeae (FA19) was found to be highly sensitive to the bactericidal activity of normal human serum (NHS). Both strain FA5100 and an unrelated serum-sensitive clinical isolate (F62) were killed by NHS via the classical complement pathway since killing required C2 and Ca++. However, the fact that only strain FA5100 was sensitive to human hypogammaglobulinemic and cord serum suggested that this strain might activate the classical complement pathway in the absence of antibody. Anticomplementary concentrations of LPS from strain FA5100 inhibited the bactericidal activity of NHS against either strain FA5100 or strain F62. However, concentrations of LPS from strain FA5100 that exhibited marginal anticomplementary behavior also inhibited the killing of strain F62 by NHS. The ability of LPS from strain FA5100 to inhibit the bactericidal activity of NHS against strain FA5100 and to activate complement was reduced by treatment with mild alkali. However, alkali-treated LPS from strain FA5100 still inhibited the bactericidal activity of NHS against strain F62.

Agammaglobulinemia↗
PubMed1987

Serum lectin with known structure activates complement through the classical pathway.

Serum mannan-binding protein (MBP), a lectin specific for mannose and N-acetylglucosamine, was revealed to activate the complement system as measured by passive hemolysis using sheep erythrocytes coated with yeast mannan. In contrast, rat liver MBP, which shares many properties in common with serum MBP, could not activate complement at all. The activation by serum MBP was inhibited effectively by the presence of haptenic sugars and dependent absolutely upon the presence of C4, indicating that the activation is initiated by the sugar binding activity of MBP and proceeds through the classical pathway. The 25 NH2-terminal amino acid sequence of rat serum MBP determined in this study was completely matched with that of MBP-A deduced from cDNA sequence by Drickamer et al. (Drickamer, K., Dordal, M. S., and Reynolds, L. (1986) J. Biol. Chem. 261, 6878-6887), revealing that MBP-A is in fact identical with serum MBP. On the basis of the knowledge of primary structures and physicochemical properties of rat serum and liver MBPs, a possible mechanism of the complement activation by serum MBP is discussed with reference to close similarity in the gross structures of serum MBP and C1q.

Animals↗