SEARCH · PubMed Health

Results for “Complement Pathway, Alternative”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85Linked to original sources

PubMed1992

Participation of complement in the phagocytosis of the conidia of Aspergillus fumigatus by human polymorphonuclear cells.

Nonspecific immunity plays a major role in the clearance of the opportunistic fungal pathogen, Aspergillus fumigatus. However, the mode of recognition of Aspergillus conidia by the different elements of an intact phagocyte system remains poorly understood. This study concentrated on the initial interaction between infective conidia and human polymorphonuclear cells (PMNL) using a double-label immunofluorescent method. At 37 degrees C, association was rapid. Although ingestion rates were slower than association, both association and ingestion plateaued at 90 min and were considerably reduced in the presence of fetal calf serum. In the presence of autologous plasma, association increased as the conidia-to-cell ratio increased, but the percentage of associated conidia that were ingested decreased. At 4 degrees C, phagocytosis was negligible. Phagocytosis experiments in the presence of plasma treated in various ways to inhibit the complement pathways demonstrated that optimal association was dependent on an active alternative complement pathway.

Analysis of Variance↗

PubMedDate not supplied

Inhibition of complement by gold sodium thiomalate.

The effect of gold sodium thiomalate on C3 and factor B activation by monosodium urate monohydrate (MSUM) and zymosan was studied using a quantitative immunoelectrophoretic assay for complement activation. C3 and factor B conversion by the classical pathway activator MSUM, was inhibited 50% and 100% by 3.2 x 10(-4)M and 10(-3)M gold sodium thiomalate, respectively. C3 and factor B conversion by the alternative pathway activator, zymosan, was much less susceptible to inhibition by gold. Gold at 10(-3)M, inhibited alternative pathway activation by only 30%. A 50% inhibition would have required 10(-2)M gold. There was no significant inhibition of complement activation through either pathway by less than 10(-4)M gold. Sodium thiomalate alone showed no inhibition. Studies using other crystals and immune complexes were confirmatory. Thus, there was no appreciable inhibition of the complement system at concentrations of gold attainable in the serum of patients receiving chrysotherapy. The in vivo significance of these findings is unknown.

Complement C3↗

PubMed2004

A study of the xenoantigenicity of adult pig islets cells.

BACKGROUND: The pig pancreas is considered to be the most suitable source of islets for xenotransplantation into patients with type I diabetes. The purpose of this study was to assess the antigenicity of pig islets, including the Galalpha1-3Galbeta1-4GlcNAc-R (the alpha-Gal) and Hanganutziu-Deicher (H-D) antigens, and the pathway involved in human complement activation. METHODS: The expression of alpha-Gal on islets from adult pigs was investigated by immunohistochemical staining and flowcytometric analysis. The alpha1,3 galactosyltransferase (alpha1,3GT) activity of islets was determined by high-performance liquid chromatography. Antigenicity to human natural antibodies, including the H-D antigen of pig islets was next examined by treatment of pig islets with tunicamycin, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and/or neuraminidase. In addition, complement-mediated islets lysis was examined using factor D-deficient and C1-deficient sera. RESULTS: Adult pig islets expressed negligible amounts of alpha-Gal epitope, and alpha1,3GT activity was also undetectable. However, human natural antibodies, immunoglobulin G and M, and the anti H-D antibody react to the adult islet. Treatment of pig islets with tunicamycin, but not PDMP, led to a drastic reduction in antigenicity to human serum, indicating the importance of N-linked sugars on the islets. Neuraminidase treatment indicated the presence of, not only the H-D antigen, but also other sialic acid antigens that reacted with the human natural antibody. The complement deposition of C4, C3 and factor B on islets was demonstrated. The alternative pathway-mediated pig islet killing accounted for approximately 30% of that by the total complement pathway. CONCLUSION: The origin of antigenicity of pig islets is mainly N-linked sugars including sialic acid antigens, but not the alpha-Gal, and pig islets can be injured by both the classical and the alternative complement pathway in human serum.

ABO Blood-Group System↗

PubMed2005

Murine complement C4 is not required for experimental autoimmune encephalomyelitis.

In vitro studies have demonstrated that myelin and myelin-derived proteins activate both the classical and alternative complement pathways. More recently, studies have shown that mice deficient in factor B, a protein required for activation of the alternative pathway, have attenuated experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. The relative contribution of the classical pathway to the pathogenesis of EAE has remained unexplored. To address this question, we performed EAE using mice deficient in C4 (C4-/-), a protein required for full activation of the classical pathway. We found that deletion of the C4 gene does not significantly change either the time of onset or the severity and tempo of myelin oligodendrocyte-induced EAE compared with controls with a fully intact complement system. We observed similar levels of cellular infiltration (CD11b+ macrophages and CD3+ T cells) and demyelination in the two kinds of mice. Despite this, ribonuclease protection assays demonstrated a two- to fourfold increase in several pro-inflammatory cytokines in C4-/- mice with EAE, including interleukin-beta (IL-1beta), IL-18, tumor necrosis factor-alpha (TNF-alpha), IP-10, and RANTES. These results support the conclusion that the contribution of murine complement to the pathogenesis of demyelinating disease is realized via the alternative pathway.

Animals↗

PubMed2000

Sublytic complement attack increases intracellular sodium in rat skeletal muscle.

BACKGROUND: Although excessive complement activation and deranged sodium homeostasis in skeletal muscle are characteristic in sepsis, their relationship has not been examined. This study was designed to determine if sublytic complement activation can directly mediate changes in myocellular sodium content. MATERIALS AND METHODS: Fast-twitch extensor digitorum longus muscles were freshly isolated from infant rats. Unsensitized muscles were incubated at 30 degrees C for 60 min in the media containing 10% human or rat serum under conditions of no complement activation, activation by zymosan, inactivation by heat, C7 or C9 deficiency, selective inhibition of complement pathway, and inhibition of Na(+)-K(+) ATPase by ouabain. Intracellular sodium ([Na(+)](i)) and potassium ([K(+)](i)) contents of the muscles, myocellular ATP, and LDH release from the muscles were then determined. RESULTS: Normal human serum significantly increased [Na(+)](i) and the [Na(+)](i)/[K(+)](i) ratio in the muscles as well as zymosan-activated serum. Heat inactivation, C7 deficiency, and inhibition of the alternative pathway completely abolished the cationic changes. Average LDH release was identical in all groups and less than 6%. Complement activation did not impair ouabain-sensitive Na(+)-K(+) ATPase activity in the muscles or alter myocellular ATP. Thus, the observed alterations are not likely due to dysfunction of Na(+)-K(+) pump or depletion of myocellular energy. Instead, alterations in [Na(+)](i) were dependent upon the amount of C9 added to C9-deficient serum, which suggests that the alterations are likely dependent on transmembrane pores created by membrane attack complexes (MAC). CONCLUSIONS: Sublytic amounts of MAC formed as a result of complement activation can directly alter [Na(+)](i) in ex vivo skeletal muscle.

Adenosine Triphosphate↗

PubMed1980

Herpes gestationis associated with the C3 nephritic factor.

Herpes gestationis (HG) is a rare, blistering disease of pregnancy and the puerperium that has immunologic findings of C3 with or without IgG deposited in a linear, band-like distribution along the dermoepidermal basement membrane zone (BMZ). A circulating IgG factor has been demonstrated that will fix complement by the classic pathway in vitro. This study involves a patient who had classic HG with C3 at the BMZ, and who had a circulating factor with activity via the alternative complement pathway similar to the previously described C3 nephritic factor found in patients with partial lipodystrophy, systemic lupus erythematosus, and membranoproliferative glomerulonephritis. Like the C3 nephritic factor, the activity was detected in IgG fractions of serum samples.

Adult↗

PubMed1991

Streptavidin-induced lysis of homologous biotinylated erythrocytes. Evidence against the key role of the avidin charge in complement activation via the alternative pathway.

It is shown that non-covalent attachment of streptavidin, as well as of avidin, to biotinylated human erythrocytes induces homologous hemolysis by complement. Rabbit antiserum against human C3 is found to inhibit the lysis specifically as compared with non-immune rabbit serum. Efficiency of lysis inhibition is greater for avidin- and streptavidin-induced lysis of biotinylated human erythrocytes than for antibody-sensitized sheep erythrocytes. In contrast to positively charged avidin (pI 11), streptavidin is a neutral protein. Hence, hemolysis of streptavidin-carrying erythrocytes is inconsistent with the suggestion on the crucial role of avidin charge in lysis. Membrane alterations (cross-linking and clusterization of biotinylated components) induced by avidin (streptavidin) seem to be a more plausible explanation for the lysis.

Avidin↗

PubMed1986

Repressed classical complement pathway activities and clinical correlations in chronic lymphocytic leukaemia.

Haemolytic activities of the classical and alternative complement pathways, and levels of C1, C4, C3, factor B and C1 inhibitor (C1-INH) were measured in 137 serum samples of 69 patients with chronic lymphocytic leukaemia (CLL). In most sera IgG, IgA and IgM concentrations were determined as well. Clinical correlations of these laboratory parameters have been studied. C1 and C4 activities were found to be depressed in almost 50% of the sera tested, and hypogammaglobulinaemia was observed with a similar frequency. Low C1 and C4 levels were found mainly in the early stages of the disease. A strong association between the occurrence of infections and hypogammaglobulinaemia was observed, although low immunoglobulin levels frequently occurred in patients without a history of infections. Low C1 and C4 levels were significantly correlated with the incidence of infections, too, and this correlation was observed mostly in the early stages of the disease. The reason for this is not known. The present results suggest that not only low immunoglobulin levels but low C1 and/or C4 levels may contribute to the increased susceptibility to infections in patients with chronic lymphocytic leukaemia.

Complement Activation↗

PubMed1981

Complement-inhibiting and anti-inflammatory properties of chlorazole fast pink 2BL.

Chlorazole fast pink 2BL inhibited the classical complement pathway in rat serum both in vivo and in vitro. The in vitro potency of chlorazole fast pink against the alternative pathway could not be assessed accurately but it was clearly less than that against the classical pathway. The compound appears to bind strongly to albumin with a resulting decrease in potency in undiluted as compared to diluted serum. Anti-inflammatory activity was observed in models of inflammation known to be highly complement-dependent (direct passive Arthus, zymosan oedema) but not in models in which complement is not involved (dextran oedema) or plays a minor role (carrageenan oedema).

Animals↗

PubMed1985

[Glomerulonephritis secondary to ventriculo-atrial shunts].

The authors report the case of a 45 year old man who had undergone a ventriculo-atrial CSF shunt procedure 5 years previously for normal pressure hydrocephalus and who had several unexplained episodes of infection over a 12 months period and has now developed a mixed nephrotic syndrome associated with a septicaemia. Corynebacterium commensale and Staphylococcus epidermis were isolated from the valve culture. Ablation of the valve resulted in clinical cure with minimal functional renal sequellae. The initial renal biopsy showed type I proliferative glomerulonephritis with subendothelial deposits of complement and immunoglobulins, which did not completely regress after 3 months' evolution. The serum complement fractions suggested activation of the alternate pathway and the possible pathogenic role of circulating immune complexes.

Antigen-Antibody Complex↗

PubMed1995

Classical complement pathway activation on nucleated cells. Role of factor H in the control of deposited C3b.

The restriction of alternative complement pathway activation in fluid phase or on nonactivator surfaces has been described as the major physiologic function of the complement regulatory protein factor H. In this study, we provide evidence that factor H is also a restriction factor of classical pathway activation on the surface of nucleated cells. We found that C3b was rapidly converted to inactivated C3b (iC3b) on human SK-MEL-93-2 melanoma cells after classical pathway activation with the murine monoclonal IgG3 Ab R24 directed against the disialoganglioside surface Ag GD3. The SK-MEL-93-2 cells are nonactivators of the alternative pathway and express neither CR1 (CD35) nor the C3b-cleaving protease p65. The cells are further characterized by the expression of only moderate amounts of DAF (CD55) and approximately 5 x 10(3) MCP (CD46) molecules/cell. FACS analysis and direct quantitation using [125I]factor H revealed high level binding of factor H to the melanoma cells (5.6 x 10(6) molecules/cell) during classical pathway activation. The binding of factor H could be inhibited under conditions that inactivate the classical complement pathway (EGTA and heat treatment), but not by factor B depletion of the serum, demonstrating that classical pathway activation was responsible for factor H binding. Treatment of factor B-depleted serum with neutralizing concentrations of polyclonal anti-factor H resulted in the prolonged presence of intact C3b on the cells and a significantly reduced generation of iC3b. The increased amount of C3b on these cells correlated with a 2.65-fold greater rate of cell death. In contrast, the increase in cell death effected by neutralizing concentrations of anti-CD46 or anti-CD55 Ab was only 0.13- or 0.35-fold, respectively. In addition, the supplementation of serum with purified factor H decreased the extent of lysis of the cells. Collectively, these data provide experimental evidence that factor H, through its cofactor activity for C3b degradation, is involved in the restriction of the classical pathway of complement on the surface of nucleated cells, a function that to date has been exclusively attributed to the membrane regulatory proteins CD35 and CD46.

Complement Activation↗

PubMed1994

Effect of some hydroxycoumarins on complement-mediated hemolysis in human serum.

Coumarin derivatives are known to possess antiinflammatory and antimetastatic properties due to their direct action on cells, predominantly on macrophages. In the present study the interactions between esculin, esculetin, fraxin, fraxetin, as well as their acetylated and methylated derivatives and non-cell system participating in inflammatory processes, comprised of serum complement proteins, were investigated in vitro. 7-Methylesculin, esculin 5Ac and esculetin 2Ac exhibited good inhibition on classical pathway (CP) activity and scoparone strongly reduced alternative pathway (AP) activity in normal human serum (NHS). Some of the hydroxycoumarins were able to enhance hemolysis. Seven derivatives were tested in C1 and C3 functional assays, as 7-methylesculin appeared to be the strongest inhibitor of both activities. Esculin (En) and scopoletin (St) altered the effect of other complement activators (heat aggregated IgG, suramin, and zymosan) when applied with them simultaneously in vitro.

Buffers↗

PubMed2000

Deficiency of human complement factor I associated with lowered factor H.

Deficiencies of factor I and/or factor H result in an increased consumption of C3 and higher susceptibility to recurrent infections. Here we describe a case of human factor I deficiency and lowered factor H levels. C3 concentration was 50% lower than normal, the classical pathway-dependent hemolytic activity was reduced to almost 30% of normal, and alternative pathway-dependent activity was completely absent. The killing by peripheral leukocytes of Candida albicans treated with deficient serum and the production of complement-dependent chemotactic factors were reduced in the proband's serum when compared with normal serum. Finally, we observed that C3 antigen present in the proband's serum has a different electrophoretic mobility than native C3 (most likely C3b), confirming the deregulation of complement activation due to the lack of regulatory proteins factors I and H. The impaired complement system described in this case, the first of its kind described in a Chile, explains the higher susceptibility to infections found in the proband.

Animals↗

PubMed1984

Complement activating cryoglobulins in the nephritis of systemic lupus erythematosus.

Complement activation in vitro by cryoglobulins isolated from the sera of 28 patients with systemic lupus erythematosus (SLE) was examined by incubating the cryoglobulin with normal human serum and performing crossed-immunoelectrophoresis of the mixture to detect C3 conversion. Eighteen of the 28 SLE cryoglobulins activated complement; eight by the classical pathway, four by the alternative pathway exclusively, and six by both pathways. In contrast only two out of 20 cryoglobulins isolated from the sera of normal subjects activated complement and both did so by the classical pathway. Twenty-three of the 28 SLE sera activated complement and complement activating cryoglobulins were isolated from 15 of these 23 sera. The parent sera of cryoglobulins activating complement had lower C4 and C3 concentrations than sera whose cryoglobulins did not split complement but these differences were not significant. The ability of SLE cryoglobulins to activate complement in vitro suggests that these immune complexes activate complement in vivo and thus may contribute to tissue damage in this disease. The activation of both classical and alternative complement pathways is in keeping with other evidence that both pathways are involved in SLE.

Adult↗

PubMed1980

Immunochemical quantitation of complement components of Clq and C3 in sera and synovial fluids of patients with bone and joint diseases.

The amount of the initiating complement component (Clq) in the classical pathway and the first essential component (C3) in the alternative complement pathway were measured with a single radial immunodiffusion (SRID). A high ionic strength was used corresponding to that of 0 . 25 M NaCl and 0 . 01 M EDTA to avoid nonspecific binding of Clq with immune aggregates. Measurements were made on sera and/or synovial fluids from 165 patients with various bone and joint diseases. Values of Clq and C3 in synovial fluids were also expressed as ratios to that of albumin in the same specimens to avoid the influence of differences in volume of synovial fluid in various diseases, and this appeared to provide a reliable index reflecting pathological conditions. Both serum Clq and C3 levels were raised highly in rheumatoid arthritis, gout, and osteomyelitis, but the extent of the elevation of C3 was less conspicuous. Values of Clq and C3 in synovial fluids also markedly increased in rheumatoid arthritis.

Adolescent↗

PubMed1998

Coelomocytes express SpBf, a homologue of factor B, the second component in the sea urchin complement system.

A homologue of factor B, SpBf, has been cloned and sequenced from an LPS-activated coelomocyte cDNA library from the purple sea urchin, Strongylocentrotus purpuratus. The deduced amino acid sequence and domain structure show significant similarity to the vertebrate Bf/C2 family proteins. SpBf is a mosaic protein, composed of five short consensus repeats, a von Willebrand Factor domain, and a serine protease domain. It has a deduced molecular mass of 91 kDa, with a conserved cleavage site for a putative factor D protease. It has ten consensus recognition sites for N-linked glycosylation. Amino acids involved in both Mg2+ binding and in serine protease activity in the vertebrate C2/Bf proteins are conserved in SpBf. Phylogenetic analysis of SpBf indicates that it is the most ancient member of the vertebrate Bf/C2 family. Additional phylogenetic analysis of the SCRs indicates that five SCRs in SpBf may be ancestral to three SCRs, which is the typical pattern in the vertebrate Bf/C2 proteins. RNA gel blots show that SpBf transcripts are 5.5 kb and are specifically expressed in coelomocytes. Genome blots suggest that the SpBf gene (Sp152) is single copy gene per haploid genome. This is the second complement component to be identified from the sea urchin, and, with the sea urchin C3 homologue, these two components may be part of a simple complement system that is homologous to the alternative pathway in higher vertebrates.

Amino Acid Sequence↗

PubMed1984

Immunological mechanisms of reactions to macromolecular solutions.

Hypersensitivity reactions to intravenous macromolecular solutions are an exacerbation of the organism defence mechanisms with production of exaggerated and deleterious effects. The immediate adverse reactions to drugs (anaphylaxis) have clinical manifestations-due to histamine release principally: cutaneous (rash, urticaria, edema); pulmonary (bronchospasm), and cardiovascular (hypotension, collapse, cardiac arrest); their intensity may be graded in degrees I to V. These reactions may be either truly anaphylactic (immunological): hypersensitivity type I with reaginic antibodies (IgE), requiring previous exposure to the drug (true allergy); other immune responses with antigen-antibody (IgG or IgM) complexes activating classical complement pathway; or anaphylactoid; indirect histamine release by direct activation of C3 (alternate complement pathway) direct histamine release by pharmacological effect; dose related effects. The incidence of reactions to plasma substitutes vary greatly according to authors. In most cases, gelatin derivatives act by direct action on mast cells (histamine release) and indeed prevention of reaction with antihistamines is effective; antibody related reactions occasionally occur (immune complexes). With dextrans, soluble immune complexes aggregates have been described; dextrans may react to specific antibodies (possibly previously produced by bacterial polysaccharides); complement activation occur only in severe reactions. HES is comparable to dextran, antibodies have been described. Other factors may predispose to anaphylactoid reactions such as genetic factors (atopy, primary complement anomalies) underlying immune processes and stress. All macromolecular solutions carry the risk of anaphylactoid side-reactions, the mechanisms of which are not completely clarified.

Anaphylaxis↗

PubMed1983

Mathematical studies of complement activation.

Kinetic studies of complement activation were followed by hemolytic assay. Mathematical analysis shows that the curve is composed of two exponents: the first one, which occurs during a short span of time, represents the classical pathway, the second the alternative pathway. We were therefore able to foretell the respective participation of each activator used: inulin, zymosan, and aggregated immunoglobulins.

Complement Activation↗