Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C5”

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

Studies of human C5a as a mediator of inflammation in normal human skin.

C5a is an 11,000-D fragment of the fifth component of complement (C5) with potent anaphylatoxic and leukocyte chemotactic activities. C5a is believed to play an important role in the pathophysiology of certain skin disorders and systemic diseases with cutaneous manifestations. However, there is very little known about the in vivo reactivity of C5a in man. In this study we examined the effects of intradermal injections of human C5a in 17 normal volunteers. C5a was prepared by interacting highly purified human C5 with zymosan bound alternative pathway C5 convertase under conditions resulting in consumption of approximately 90% of the C5 substrate. C5a produced in this manner was chemotactic for human neutrophils and monocytes (0.5 X 10(-7) to 10(-9) M) and caused neutrophil aggregation and myeloperoxidase release (concentrations greater than or equal to 10(-10) M) in vitro. In vivo, C5a produced immediate wheal and flare reactions in all volunteers, and was active in doses as low as 1 ng (10(-13) mol). Intradermal testing with 20 ng of C5a in eight volunteers produced a maximal mean wheal of 11.75 mm (+/- 0.80 mm SEM) 20 min after anaphylatoxin injection, and a maximal mean erythema of 62.50 mm (+/- 3.27 mm SEM) 10 min after C5a administration. Reactions at C5a test sites were dose-related, associated with marked pruritus in some subjects, resolved without lesion formation, and were not associated with late phase reactions. In vivo testing revealed that human C5a was a more potent mediator of wheal and flare reactions than histamine, 48/80, human C3a, or morphine sulfate. Skin biopsies from eight volunteers 20 min after intradermal injection of 20 ng of C5a revealed a neutrophil-predominant perivascular infiltrate, endothelial cell edema, and sites of leukocytoclasis. Mast cell degranulation was observed on both light and electron microscopy of biopsies from C5a test sites. Although erythema at C5a injection sites was reduced by pretreating volunteers with hydroxyzine, whealing reactions and cellular infiltrates in biopsies were unaffected by this H1-antihistamine. Moderate doses of systemic corticosteroids did not alter clinical or histologic reactions at C5a injection sites in two volunteers. This study, using doses within the potential physiologic range of the anaphylatoxin, provides a comprehensive assessment of the effect of human C5a on normal human skin.

Adult↗
PubMed1979

Generation of biologic activity from the purified alpha-chain of C5.

The alpha- and beta-chains of the fifth component of human complement (C5) have been isolated and their physical and biologic properties have been characterized. After electrophoresis in SDS-poly-acrylamide slab gels, the chains were eluted from the gels and extensively dialyzed. The amino acid composition of each chain was then determined. On SDS-gels, the alpha-chain was PAS positive whereas the beta-chain revealed little or no staining. As a measure of chemotactic activity, the lysosomal enzyme-releasing activity of both chains was examined before and after trypsinization; activity resided almost entirely in the alpha subunit. Reconstitution of C5 from its isolated chains, followed by trypsinization resulted in slightly less activity than that from the individual alpha subunit. These findings provide direct support for previous evidence suggesting the biologic activity for neutrophils derives entirely from the alpha subunit of C5. This represents the first report of direct recovery of biologic activity from a purified subunit chain of C5.

Alkylation↗
PubMed1977

Hereditary C5 deficiency in man. III. Studies of hemostasis and platelet responses to zymosan.

Platelet-rich-plasma from two hemostatically normal individuals, genetically lacking the fifth component of complement (C5), failed to exhibit normal platelet aggregation, or serotonin release, in the presence of zymosan. This abnormality was found to reside in the C5D plasma rather than in the platelets as demonstrated by the inability of the deficient plasma to activate zymosan for the aggregation of washed normal platelets. The defect could be corrected by the addition of normal plasma, normal serlm, or highly purified human C5. A plasma abnormality similar to that found in the C5D individuals was also noted in plasmas deficient in C3, C6, and C7; whereas C8 plasma D behaved normally. These data suggest that this platelet reaction requires late acting C components, perhaps as the C567 complex, bound to the zymosan particles.

Blood Platelets↗
PubMed1987

Complement activity in normal rabbit bronchoalveolar fluid. Description of an inhibitor of C3 activation.

Hemolytically active C4, C3, C5, and C6, and trace amounts of C1, were present in bronchoalveolar lavage fluid from healthy adult rabbits. Both the alternative and classical pathways were functionally intact through C5. Complement depletion by intravascularly administered cobra venom factor caused a parallel decrease in lavageable C5 from the rabbit's lungs. Whereas BALF C5 had specific activity comparable to serum C5, that of BALF C3 was lower than predicted. This was found to be due to the action of a substance that selectively blocked C3 activation. The inhibitor did not cause irreversible inactivation of C3, and it had no effect on C5 activity. It blocked the formation of EAC423 from EAC42 + C3, but not the lysis of preformed EAC423 + C5-9 or EAC423 rosetting with rabbit neutrophils. Hydrophobic chromatography of BALF separated the activity of the inhibitor from that of C3. Further chromatography showed that it had a net negative charge at physiologic pH, and molecular weight between 14 and 30 kilodaltons. The presence of an inhibitor of C3 activation in the airways would provide control of complement activation in an environment that is constantly exposed to bacteria, dust, and other potential inflammatory stimuli.

Animals↗
PubMed1976

Hereditary deficiency of the fifth component of complement in man. I. Clinical, immunochemical, and family studies.

The first recognized human kindred with hereditary deficiency of the fifth component of complement (C5) is described. The proband, a 20-year-old black female with systemic lupus erythematosus since age 11, lacked serum hemolytic complement activity, even during remission. C5 was undetectable in her serum by both immunodiffusion and hemolytic assays. Other complement components were normal during remission of lupus, but C1, C4, C2, and C3 levels fell during exacerbations. A younger half-sister, who had no underlying disease, was also found to lack immunochemically detectable C5. By hemolytic assay, she exhibited 1-2% of the normal serum C5 level and normal concentrations of other complement components. C5 levels of other family members were either normal or approximately half-normal, consistent with autosomal codominant inheritance of the gene determining C5 deficiency. Normal hemolytic titers were restored to both homozygous C5-deficient (C5D) sera by addition of highly purified human C5. In specific C5 titrations, however, it was noted that when limited amounts of C5 were assayed in the presence of low dilutions of either C5D serum, curving rather than linear dose-response plots were consistently obtained, suggesting some inhibitory effect. Further studies suggested that low dilutions of C5D serum contain a factor (or factors) interfering at some step in the hemolytic assay of C5, rather than a true C5 inhibitor or inactivator. Of clinical interest are (a) the documentation of membranous glomerulonephritis, vasculitis, and arthritis in an individual lacking C5 (and its biologic functions), and (b) a remarkable propensity to bacterial infections in the proband, even during periods of low-dose or alternate-day corticosteroid therapy. Other observations indicate that the C5D state is compatible with normal coagulation function and the capacity to mount a neutrophilic leukocytosis during pyogenic infection.

Adult↗
PubMed1987

Generation of a monoclonal antibody to mouse C5 application in an ELISA assay for detection of anti-C5 antibodies.

We have generated a monoclonal antibody with specificity for the fifth component of mouse complement (C5). This antibody precipitates the two chains of C5 from normal mouse serum and inhibits C5-dependent hemolysis in a functional complement test. In this study we describe its application in an enzyme-linked immunoadsorbent assay (ELISA assay) for the detection of anti-C5 antibodies in serum. Monoclonal anti-C5 coupled to wells of an ELISA plate specifically binds C5 from unfractionated normal mouse serum. This subsequently serves as antigen to bind anti-C5 serum antibodies. By this approach we have circumvented the need for extensive purification of C5 from serum which would be required if C5 was directly coupled to ELISA plates as antigen. Serum antibodies from C5-immunized mice bound with high avidity to wells containing normal serum as antigen source in amounts representing 1 microgram to 250 ng C5. There was no antibody binding to wells containing C5-deficient serum as antigen source. The immune reaction was detected by development with enzyme-coupled goat-anti mouse Ig antibodies specific for various mouse Ig subclasses. This method allows the qualitative characterization of immune responses to mouse C5 which is an ideal model for a natural self antigen in studies of immunological tolerance.

Animals↗
PubMed1985

Role of C5 and recruited neutrophils in early clearance of nontypable Haemophilus influenzae from murine lungs.

We used a mouse model system to investigate the pulmonary defense mechanisms involved in clearance of nontypable Haemophilus influenzae from the lower respiratory tract. The importance of the C5 complement protein molecule in polymorphonuclear leukocyte (PMN) recruitment was studied by using congenic C5-sufficient B10.D2/nSn (C5+) and C5-deficient B10.D2/oSn (C5-) mice. The C5+ and C5- mice were inoculated with saline or nontypable H. influenzae via an endobronchial catheter. Clearance of bacteria was studied by using quantitative lung cultures. Bronchoalveolar lavage was performed at several time intervals. The number of cells in the lavage fluid were counted, and chemotactic activity was assayed in lavage fluid by the leading front technique, using human PMN in modified Boyden chambers. Pulmonary clearance of bacteria was significantly impaired in the absence of C5 (P less than 0.05). The C5+ mice recruited significantly more PMN after challenge with nontypable H. influenzae than C5- mice did (P less than 0.05), but significant PMN recruitment occurred in C5- mice. Similarly, although chemotactic activity was present in both C5+ and C5- mice, significantly more intraalveolar chemotactic activity was noted in C5+ mice than in C5- mice (P less than 0.05). The C5 molecule yields important chemotaxins during this early time period, but other chemotaxins are also present within the alveoli, demonstrating the redundancy of the inflammatory response after pulmonary challenge with nontypable H. influenzae. Nitrogen mustard-induced neutropenic animals were studied to evaluate the functional importance of PMN in pulmonary clearance of nontypable H. influenzae. Pulmonary clearance of nontypable H. influenzae was significantly impaired in neutropenic animals (P less than 0.05). Our results indicate that the prompt appearance of PMN in lungs is crucial for early clearance of nontypable H. influenzae.

Animals↗
PubMed1977

Hereditary C5 deficiency in man: genetic linkage studies.

Genetic linkage studies were performed on the only reported kindred with genetic deficiency of the fifth component of complement (C5). Thirty family members in four generations were studied for C5 defiency and 32 genetic marker systems. Of these marker loci, 13 were informative in this pedigree. Most importantly, C5 deficiency was excluded (lod score greater than -2.0) from linkage with the major histocompatibility locus (HLA) from a recombination frequency of greater than 15% (in females). Other marker systems excluded from linkage with C5 deficiency included the ceruloplasmin and Duffy loci at a recombination frequency of less than 15%, and the erythrocyte glyoxalase, MN, and Lewis loci at a recombination frequency of less than 5%. The most positive lod score (1.07, theta=0.05) was for linkage between C5 and haptoglobin, but this score does not reach statistical significance. Thus, among the genes for complement components which can be mapped because of deficiency states or polymorphic gene products, C5 joins C1r, C3 and C6 in not being closely linked to HLA. In contrast, close HLA linkage has been demonstrated for C2, C4, properdin factor B and, in one of two families, C8.

Adolescent↗
PubMed1977

Metabolism of the fifth component of complement, and its relation to metabolism of the third component, in patients with complement activation.

The metabolism of the fifth component of complement (C5), and its relatonship to metabolism of the third component of complement (C3), has been studied in normal subjects and patients by simultaneous administration of radioiodine labeled C5 and C3. In seven normal subjects the fractional catabolic rate of C5 ranged from 1.5 to 2.1% of the plasma pool/h and extravascular/intravascular distribution ratio from 0.22 to 0.78, these values being similar to those obtained for C3, and synthesis rate from 71 to 134 mug/kg per h, In patients with complement activation the increase in fractional catabolic rate of C5 was nearly always less than that of C3. The data also showed that there was increased extravascular distribution of C3 and C5 in most patients and considerable extravascular catabolism of both proteins in some. However, there were differences in metabolic parameters between patients with different types of complement activation. In patients with systemic lupus erythematosus, fractional catabolism and extravascular distribution of C3 and C5 were both increased, and there was marked extravascular catabolism of both proteins. There was increased fractional catabolism and extravascular distribution of C3 in patients with mesangiocapillary nephritis and (or) partial lipodystrophy, and fractional catabolism of C5 was also increased in three of six studies although distribution of C5 was always within the normal range; however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated.

Adolescent↗
PubMed1985

Isolation of human complement factors C3, C5 and H.

An improved method for simultaneous purification of complement factors C3, C5 and H from human plasma has been developed. Using an initial batch separation technique with QAE-Sephadex, followed by chromatography on SP-Sephadex and gel filtration in Sephadex G-200, 600 mg of highly pure C3 can be prepared from 1600 ml of plasma. Simultaneously about 70 mg of highly pure factor H and 30 mg of C5 are obtained by chromatography of post SP-Sephadex material on DEAE-Sephacel. A small amount of C3 in the C5 pool is removed by anti-C3-Sepharose. By maleylation or citraconylation of reduced and alkylated C3, the constitutive polypeptide chains are modified in a way that made them separable by ion exchange chromatography.

Chromatography, Gel↗
PubMed1986

A study on location of synthetic site which mainly synthesizes and delivers fifth component of complement system in vivo.

Tissue sites for synthesis of the fifth component of complement (C5) in vivo have been investigated by using allogeneic bone marrow chimeras and bone marrow chimeras which were transplanted in addition with hepatocytes. Our prior studies have demonstrated that bone marrow chimeras which had been prepared by transplanting marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients lacked detectable levels of C5 in the sera. However, when such potentially C5-deficient [C5(+)---C5(-)] chimeras were introduced into their spleens by means of injections of fully dispersed single cell suspensions of hepatocytes isolated from the C5-sufficient donor strain, they accepted the transplantation of hepatocytes for prolonged periods and developed a measurable amount of C5 in the sera. These results indicate that C5 protein in sera is not synthesized in significant amount by cells that are descendants of bone marrow cells but rather that this complement component is synthesized and delivered to the blood in vivo by somatic cells including liver cells that are not derivatives of the bone marrow.

Animals↗
PubMed1992

Capacity of antigen uptake by B cells, fibroblasts or macrophages determines efficiency of presentation of a soluble self antigen (C5) to T lymphocytes.

Self antigens in the body fluids must be taken up, processed and presented by antigen-presenting cells (APC) in order to induce T cell tolerance. For self antigens like the fifth component of complement (C5) which is not picked up by APC via antigen-specific receptors, presentation has to rely on uptake by nonspecific means. C5 was used as a model soluble self antigen to study the capacity of different APC (B lymphoma cells, fibroblasts and macrophages) of taking up, processing and presenting low concentrations of soluble C5 to C5 specific T cell hybrids. Under conditions of limiting antigen amounts macrophages and fibroblasts exhibited similar presentation capacity for soluble C5 while B cells did not. C5 presentation by macrophages was enhanced in the presence of C5-specific antibody and augmented further if antigen was added in the form of particulate latex-antigen-antibody complexes indicating enhanced uptake via Fc receptor-mediated endocytosis or phagocytosis. B cells presented soluble C5 only in the presence of C5-specific antibody. Uptake of C5 under these conditions occurred via Fc receptors type II. This pathway of antigen uptake did not operate with other antigens which were presented efficiently after nonspecific endocytosis. In light of these findings it seems reasonable to propose that nonspecific endocytosis of serum proteins like C5 by B cells is normally limited in order to avoid interference with their critical role in antigen receptor-mediated uptake and presentation for the initiation of an antibody response. It seems likely that presentation of soluble self antigens present in the circulation may normally be the task of dendritic cells and macrophages depending on the physical shape of the antigen.

Animals↗
PubMed1987

Passive transfer studies with type II collagen antibody in B10.D2/old and new line and C57Bl/6 normal and beige (Chediak-Higashi) strains: evidence of important roles for C5 and multiple inflammatory cell types in the development of erosive arthritis.

C5-normal B10.D2/new line mice were susceptible to passively transferred arthritis from purified type II collagen antibody, and in vitro studies demonstrated that, when bound to cartilage, this antibody readily activated complement C5 to C5a. C5-deficient B10.D2/old line mice failed to develop passively transferred arthritis, despite the deposition of antibody and C3 along the cartilage surface. C57Bl/6 mice were susceptible to passively transferred arthritis, which was characterized in histopathologic studies as an erosive synovitis involving multiple inflammatory cell types. In contrast, neither clinical nor histologic evidence of arthritis was observed in C57Bl/6 mice with the beige mutation (Chediak-Higashi syndrome).

Animals↗
PubMed1989

An intracellular self protein synthesized in macrophages is presented but fails to induce tolerance.

Mice deficient for the fifth component of murine complement (C5), unlike normal mice, do not possess the secreted form of C5 in their body fluids and can be readily immunized to serum-derived normal C5. Although macrophages from C5-deficient mice do not secrete C5, they synthesize the precursor form (pro-C5). Therefore contact of T cells with autologous pro-C5 presented by macrophages is theoretically possible. We show that macrophages from C5-deficient mice can indeed stimulate a class II restricted C5-specific T cell clone without addition of exogenous C5. Immunization of C5-deficient mice with autologous pro-C5 induces vigorous C5-specific T cell proliferation and pro-C5 is recognized by C5-specific T cells in vitro, demonstrating that this protein fails to induce tolerance under physiological conditions. Thus, intracellular pro-C5 is processed and presented by C5-deficient macrophages and can activate T cell clones in vitro, yet is neither immunogenic nor tolerogenic for T cells in vivo.

Animals↗
PubMed1989

Secretion of the terminal complement proteins, C5-C9, by human platelets.

The terminal complement components, C8 and C9, and to a lesser extent C5, C6, and C7, but minimal amounts of C3, were shown to be associated with washed human platelets. In unactivated platelets, the complement components were detected in the platelet pellet by hemolytic assays after centrifugation and disruption of the platelets by freeze-thawing. However, after platelets had been activated by collagen, thrombin, or aggregated IgG to induce aggregation, the complement components were released into the supernatant. The rank order of hemolytic activity of C9, C8, C7, C6, and C5 detected in the supernatants of activated platelets was quite different from that found in serum from the same donors, in the same assays. In particular, the serum C7 hemolytic titer was more than twice the serum C9 hemolytic titer, whereas the activity of C9 detected from platelets was more than twice that of C7. This argues against a purely nonspecific uptake of these proteins by platelets from plasma. The functional role of terminal complement components released from platelets during activation is unknown, but it is tempting to speculate that these proteins may have a role in platelet-dependent immunological tissue injury. Because the C5b-9 membrane attack complex activates platelets, it is possible that release of terminal complement proteins serves to amplify platelet activation and may also play a role in diseases in which complement membrane attack complexes have been implicated.

Blood Platelets↗
PubMed1977

Yeast opsonization defect and immunoglobulin deficiency in severe infantile dermatitis (Leiner's disease).

The defect in Leiner's disease, which presents in early infancy with extensive dermatitis, diarrhoea, and failure to thrive, has been attributed to a defect of the fifth component of complement (C5). We report 2 brothers with extensive dermatitis and dysgammaglobulinaemia. Both died. The older showed symptoms of Leiner's disease: C5 tests were not performed. The younger had extensive dermatitis and was found to have the C5 defect. He developed normally, but died suddenly with pertussis. We postulate that the C5 defect is not the sole cause of Leiner's disease as has been suggested, but that hypogammaglobulinaemia or other lymphoid deficiency is also required for its expression.

Agammaglobulinemia↗
PubMed1979

Deficiency of the fifth component of complement in human subjects. Clinical, genetic and immunologic studies in a large kindred.

The discovery of a large kindred with a heritable deficiency of the fifth component of complement (C5) has permitted the accumulation of new clinical, genetic and immunologic data concerning the role of C5 in human subjects. The proband, who has had nine episodes of disseminated gonococcal infection, has a hemolytic C5 level of approximately 0.5 per cent of normal. No C5 protein was detectable, but low levels of functional C5 activity could be found using a sensitive bactericidal assay. The proband's twin as well as another sister also had extremely low levels of hemolytic C5(approximately 0.5 per cent normal), but both these subjects have been healthy. Hemolytic complement and bacteriolytic activity could be restored by the addition of purified C5. No chemotactic activity for polymorphonuclear leukocytes could be generated in the C5-deficient serums upon activation of either the classic or alternative pathways, again demonstrating the importance of C5 in human subjects for the production of chemotactic factors. The chemotactic responsiveness of the patients' polymorphonuclear leukocytes and monocytes to preformed chemotactic factors was not depressed. Twenty-two of 32 other family members from three generations had depressed whole hemolytic complement levels. In 19 of 30 family members, levels of hemolytic C5 ranged from 13 to 64 per cent of normal. No linkage for C5 deficiency and the A or B loci of the major histocompatibility complex could be found. These data suggest an autosomal codominant mode of inheritance of C5 deficiency. Deficiency of C5 is compatible with good health, but it can be associated with repeated disseminated gonococcal infection.

Adult↗