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PubMed1985

Cardiopulmonary bypass and host defense functions in human beings: I. Serum levels and role of immunoglobulins and complement in phagocytosis.

In patients undergoing open-heart surgical procedures, the serum levels of immunoglobulins and complement were determined as well as the functional capacity of these defense proteins as opsonins to facilitate phagocytosis by polymorphonuclear leukocytes. A considerable decrease in serum levels of the proteins studied was found after cardiopulmonary bypass (CPB). As a result, the opsonic capacity of post-CPB plasma was diminished. After correction for hemodilution, however, no difference between pre- and post-CPB plasma, as measured by the activity of thermolabile (e.g., complement C3) and thermostabile (e.g., immunoglobulin IgG) opsonins, could be demonstrated. It is concluded that CPB causes a quantitative but no functional decrease in levels of IgG and C3.

Adult↗

PubMed1995

In vitro cleavage of serum complement protein C3: a comparison between patients with adult periodontitis and periodontally healthy persons.

This study tested the hypothesis that in vitro cleavage of C3 could be triggered with similar case in serum samples from patients with adult periodontitis (n = 26) as in samples from periodontally healthy subjects (n = 13). A lipoteichoic acid, a lipopolysaccharide and an aggregated IgG served as activators of complement. On the average, the periodontitis group generated significantly (p < 0.01) more C3d activation fragments than did the healthy group, as judged from rocket immunoelectrophoresis measurements. Cleavage of C4 and factor B were then assayed through immunoblotting, without prior purification of the sera. C4c fragments were seen in all activated samples, the healthy group causing significantly (p < 0.05) more C4 conversion than did the periodontitis group. Cleavage of factor B, taken as a measure of soluble amplification convertase formation, was about equal between the groups. We inferred therefore that the 2 groups produced comparable amounts of C3b. The results suggested, however, that periodontitis sera favour breakdown of the opsonin C3b, most likely by activating the regulatory proteins factor H and I. Lipoteichoic acid, causing moderate depletion of C4 and factor B, produced significantly (p < 0.01) more C3d fragments than the other two activators examined. It may be that complement activation is down-regulated in periodontitis sera, perhaps at the expense of adequate local opsonic function.

Adult↗

PubMed1982

Immunoelectron microscopic localization of immunoglobulins and complement in human renal glomeruli.

A study was undertaken to evaluate some processing variables affecting the immunoelectron microscopic demonstration of immunoglobulins and complement (C3) in human glomeruli. Percutaneous biopsies were performed on 28 patients with various types of glomerulonephritis. Light microscopic, electron microscopic, and immunofluorescence examinations were performed by routine methods. For immunoelectron microscopy, fixation in paraformaldehyde (PA) or periodate-lysine-paraformaldehyde (PLP) was used. With the diffusion technique, using tissue chopper or cryostat sections, human immunoglobulin (Ig)G, IgA, IgM, and C3 were localized in glomeruli with peroxidase-labeled antisera. Using PLP and the tissue chopper sections, good ultrastructure was achieved. The antigens could be demonstrated in intramembranous, subepithelial, subendothelial, or mesangial immune deposits. Penetration of antibodies and quality of peroxidase reaction in the cryostat sections did not differ from that of the tissue chopper sections. Freezing and thawing, however, resulted in inferior morphology. If PA was used, the antigens could not be reliably demonstrated. The results of light microscopy, electron microscopy, and immunofluorescence microscopy were in good agreement with those from the immunoperoxidase procedure. The present study shows that PLP preserves well the antigenicity of human immunoglobulins and C3, resulting in good ultrastructure. PA fixation, on the contrary, caused a loss of antigenicity before an adequate ultrastructure could be achieved.

Complement C3↗

PubMed1992

Isolation, characterization, and immunoprecipitation studies of immune complexes from membranes of beta-thalassemic erythrocytes.

beta-Thalassemia, a hemoglobinopathy that results in the precipitation of denatured alpha-globin chains on the membrane, is characterized by erythrocytes with significantly reduced lifespans. We have demonstrated previously that hemoglobin denaturation on the membrane can promote clustering of integral membrane proteins, and that this clustering in turn leads to autologous antibody binding, complement fixation, and rapid removal of the cell by macrophages. To evaluate whether this pathway also occurs in beta-thalassemic cells, we have isolated and characterized the immune complexes from the membranes of these cells. We observe that autologous IgG-containing complexes obtained by either immunoprecipitation or simple centrifugation of nondenaturing detergent extracts of beta-thalassemic cell membranes contain globin, band 3, IgG, and complement as major components. Absorption spectra of these complexes demonstrate that the globin is, indeed, mainly in the form of hemichromes. Immunoblotting studies further show that much of the band 3 protein in the aggregates is covalently cross-linked to a dimeric or tetrameric form, consistent with the preference of the autologous IgG for clustered band 3. Although the insoluble aggregates constitute only approximately 1.6% of the total membrane protein, they still contain 27% of the total IgG and 35% of the total complement C3 on the thalassemic cell surface. Because cell surface IgG and complement component C3 are thought to trigger removal of erythrocytes from circulation, the hemichrome-induced clustering of band 3 may contribute to the beta-thalassemic cell's shortened lifespan.

Anion Exchange Protein 1, Erythrocyte↗

PubMed1994

Serum and ascitic concentration of C3, C4 and protein in cirrhotic patients with spontaneous bacterial peritonitis.

BACKGROUND: Lower concentration of ascitic or serum complement (C3, C4) or protein has been reported to participate in the development of spontaneous bacterial peritonitis (SBP). In Taiwan, the etiology of hepatic cirrhosis is mainly post-hepatic and SBP is the common complication. This study aims to determine the role of protein and complements in the pathogenesis of SBP. METHODS: 119 cirrhotic patients were divided into two groups, 30 SBP and 89 non-SBP. The concentrations of ascitic and serum complement and protein were measured for comparison. RESULTS: The ascitic and serum C3, C4 and protein levels were significantly lower (P < 0.05) in patients with SBP than in non-SBP patients. No significant differences were noted in the ascites/serum ratio of C3, C4 and protein in patient with or without SBP. CONCLUSIONS: Low levels of ascitic and serum protein and complements, C3 and C4, may be prone to develop SBP in our patients mostly with post-hepatitic cirrhosis.

Aged↗

PubMed1996

Study on clinical immunity in patients with coronary artery disease.

The study was designed to assess the change in humoral immunity in patients with coronary artery disease (CAD). In 42 patients with CAD and 40 healthy controls, the serum levels of IgG, IgA, IgM and complement C3 were measured by simple immune diffusion. The results showed that: (1) the serum levels of IgG in patients with CAD were significantly higher than those in controls (14.14 +/- 2.77 g/L vs 10.16 +/- 2.86 g/L p < 0.01); (2) the serum levels of complement C3 in patients with CAD were higher than those in controls (1.52 +/- 0.67 g/L vs 1.28 +/- 0.53 g/L p < 0.05); and (3) no statistical difference in serum levels of IgA and IgM between the two groups was found. The results suggest that there was an enhanced humoral immune action in patients with CAD, and immune injury may be an important factor in the pathogenetic mechanism of CAD.

Adult↗

PubMed1985

Complement and clinical intervention.

The nine major components of the complement protein system are normally activated in sequence by antigen-antibody complexes, initiating the inflammatory response. The clinical manifestations arise mainly from the release of histamine, mediated by anaphylatoxin action on mast cells. In rampant infection, this classical pathway is enhanced by further activation of complement C3 through a specific enzyme loop, the alternative pathway. Unfortunately the complexity of the complement system makes it vulnerable to external interference, particularly to man's intervention both through the administration of intravenous "drugs" and by certain surgical procedures. This results in gross systemic activation of complement, particularly C3 giving rise to anaphylactoid shock. More recently, direct activation of complement C5 has been reported, particularly as a result of polytrauma. This has consequences on polymorphonuclear leucocyte behaviour and is likely to be involved in adult respiratory distress syndrome (ARDS). Similarly, excessive activation of C3 may stimulate disseminated intravascular coagulation (DIC) rather than immediate anaphylactoid response. The clinical outcome of complement activation appears to depend upon the rate of activation and its extent, as well as upon the particular component involved. In immediate reactions, complement may be involved in both immune and non-immune activations. Bias to certain pathways is revealed by certain drugs or procedures, and practical methods of evaluating reaction mechanisms are discussed. Despite the high incidence of complement involvement in immediate reactions, there are no useful screening pointers to the patient "at risk". Delayed effects have received little attention. Although C3 conversion is certainly associated with DIC, its predictive value in a clinical trial was not very great.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

PubMed1983

The use of C3d as a means of monitoring clinical activity in systemic lupus erythematosus and rheumatoid arthritis.

Plasma samples from 44 patients with systemic lupus erythematosus (SLE) and 43 with rheumatoid arthritis (RA) were assayed for C3d, a breakdown product of the third component of complement (C3), which was also measured in parallel. Levels of C3d varied in direct proportion with disease activity in RA, whereas C3 showed little change. Although C3d values also increased with worsening clinical condition in SLE, this trend was not considered to be sufficiently clear to be useful and did not provide any advantage over the routinely performed C3 assay.

Arthritis, Rheumatoid↗

PubMed2005

Effects of arginine supplementation on the humoral and innate immune response of older people.

OBJECTIVE: To evaluate whether oral supplementation with arginine affects the humoral and innate immune response after vaccination against Streptococcus pneumoniae in a group of people aged 60 y and older, free-living in the community. DESIGN: A randomized controlled trial with one supplemented group and one control group. SETTING: Older persons living in the community. SUBJECTS: A total of 29 adults aged 60 y and older. INTERVENTIONS: The older people were randomized into two groups, one with arginine supplementation (15 g/day) for 4 weeks after pneumococcal vaccine. The control group received only the vaccine. Anthropometric measurements and immune system function parameters: neutrophil chemotaxis and phagocytosis, natural killer cell activity, determination of serum pneumococcal polysaccharide antibodies and serum C3 and C4. RESULTS: Neutrophil phagocytosis and the serum concentration of complement (C3 and C4) did not differ between groups. IgG antibodies against pneumococcal polysaccharide serotypes 1, 5 and 6B increased in both groups. The following parameters increased in the arginine-supplemented group compared to the nonsupplemented group: neutrophil chemotaxis (34 vs 19 units of migration, P = 0.002), natural killer cell cytotoxicity (23.3 vs 13.4 10 M/Ul 40%, P = 0.011) and IgG against antigen 5 (12.3 vs 6.2 mug/ml, P = 0.044). CONCLUSIONS: This study suggests that, after the pneumococcal vaccine, the intake of arginine increased neutrophil chemotaxis, natural killer cytotoxicity and serum concentration of IgG against antigen 5 in older people. These results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. SPONSORSHIP: Supported in part by CAPES and FAEPA.

Administration, Oral↗

PubMed1984

The biochemistry of opsonization: central role of the reactive thiolester of the third component of complement.

In these studies, we have defined the mechanism by which the opsonic fragment of the third component of complement (C3) binds to pathogenic bacteria. With use of purified human C3 to reconstitute the alternative pathway in human serum in which both C3 and C4 had been chemically inactivated, we showed that opsonization of pathogenic serotypes of Streptococcus pneumoniae (serotypes 3, 4, 6A, 14, and 18C) requires the reactive thiolester of native C3. When purified human C3 (thiolester intact) is added to serum deficient in C3 and C4, phagocytic uptake of 3H-labeled pneumococci by polymorphonuclear leukocytes from normal adults is fully reconstituted. However, hydrolysis of the thiolester or reaction of the thiolester with the inhibitor methylamine abolishes opsonization and phagocytosis. Finally, by characterizing those C3 fragments released from pneumococcal surfaces after treatment with 1.0 M hydroxylamine, we have defined a role for covalent-bond formation in the opsonic interaction. Therefore, the presence of the reactive thiolester of C3 is an absolute requirement for the opsonic and covalent binding of the C3b molecule to pathogenic bacteria.

Chemical Phenomena↗

PubMedDate not supplied

[The significance of low levels of total proteins, albumins, globulins and complement factors in ascitic fluid and the development of spontaneous bacterial peritonitis in patients with liver cirrhosis].

Spontaneous bacterial peritonitis is one of the most common complications of ascitic fluid in patients with liver cirrhosis. The aim of this study was to investigate the role of total protein, albumin, globulin and complement ascitic fluid concentrations in development of spontaneous bacterial peritonitis in patients with liver cirrhosis. In patients with liver cirrhosis and spontaneous bacterial peritonitis (n = 8) the ascitic fluid total protein, albumin and globulin concentrations were significantly lower than in patients with sterile ascites (n = 11) (p < 0.01). The ascitic fluid complement C3 and C4 concentrations were significantly lower in patients with spontaneous bacterial peritonitis than in patients with sterile ascites (9.1 +/- 3.1 mg/dL to 22.9 +/- 17.4 mg/dL, p < 0.01; 3.8 +/- 5.9 mg/dL to 8.2 +/- 5.9 mg/dL, p < 0.01, respectively). The ascites total protein, albumin, globulin and complement concentrations in cirrhotic patients with spontaneous bacterial peritonitis were significantly lower than in patients with sterile ascites demonstrating the importance of those factors in ascitic fluid defense against secondary bacterial infection.

Albumins↗

PubMed2000

Secretory IgA and complement levels in patients with hookworm infection in Zaria.

As a continuing investigation into the immunological reactions involved in hookworm infection the levels of secretory IgA (sIgA). IgM, IgA, complement C3 and C4 were studied in 57 Nigerians with hookworm infection and compared with those of 28 healthy, normal controls. The hookworm patients were divided into three groups based on the degree of anaemia (Hb1-7 and hypochromia +++). Group II had moderate anaemia (Hb8-11, hypochromia ++ and Group III had no signs of anaemia despite the underlying hookworm infection. The patients also comprised those in whom hookworm was the sole infection and those with hookworm associated with other parasites. Significant differences in the results between each patient subgroup and the controls were analysed using the student t-test. IgA was significantly elevated in patients with anaemia of mild to moderate severity and in patients with hookworm only (P < 0.05) while sIgA was significantly elevated in all subgroups compared to controls (P < 0.05). IgM was significantly elevated in-patients with marked anaemia, in-patients without anaemia and in those with hookworm infection associated with other parasites (P < 0.05). The difference in IgG levels between patients and controls was not significant (P 0.1). C4 was significantly elevated in patients with marked moderate anaemia and those with hookworm only (P < 0.05) while C3 levels were not significantly different in the subgroups compared with controls. These results suggest the possibility of polyclonal B-cell activation by T-independent antigens such as the polysaccharide cuticular antigens of the hookworms and the stimulation of the classical pathway of the complement system.

Adolescent↗

PubMed1978

Alternate pathway activation of complement in a Proteus mirabilis ulceration of the cornea.

A 63-year-old patient had an extensive infiltration, ulceration, and eventual perforation of the cornea caused by Proteus mirabilis. Histopathological examination of corneal tissue that was obtained at keratoplasty disclosed that the stroma was ulcerated with a diffuse infiltration of polymorphonuclear leukocytes. Immunopathological examination of the cornea revealed prominent and diffuse staining for properdin and C3 complement. There was an absence of staining for IgG, IgA, IgM, IgE, and C4 complement. These findings suggest that the alternate pathway of complement was activated in this ulcerated cornea and that immunopathological phenomena contribute to the polymorphonuclear infiltration found with Gram-negative ulcerations of the human cornea.

Complement C3↗

PubMed1997

Immunological pattern in Syrian golden hamsters experimentally infected with Schistosoma mansoni and Leishmania d. infantum.

The immunoglobulins (IgG, IgM, IgE, & IgA) and the complements (C3 & C4) were studied in hamsters as result of a single infection (S. mansoni or L.d. infantum) and as concomitant infection (L.d. infantum on top of S. mansoni). The immunological pattern showed profound IgG and IgA increase in the concomitant group than either infection alone. Also, concomitant infection induced more IgE increase than either infection alone. On the other hand, C3 and C4 showed more decrease in concomitant infection. The whole results were discussed.

Animals↗

PubMed1986

Campylobacter jejuni bacteraemia as a cause of recurrent fever in a patient with hypogammaglobulinaemia.

In a hypogammaglobulinaemic patient with faecal cultures persistently positive for Campylobacter jejuni it was shown that C. jejuni bacteraemia was responsible for a long history of self-limiting attacks of fever. A focus of infection outside the gastro-intestinal tract was not found. Antimicrobial treatment failed to eradicate C. jejuni. Antibodies against C. jejuni were not detectable and there was also a defect in serum bactericidal activity. In contrast with normal serum, it was shown that, when patient's serum was used in tests, IgG and the components of complement C3 and C4 did not bind to C. jejuni.

Adult↗

PubMed1982

Inhibition of human lymphocyte blastogenesis by C3: the role of serum in the tissue culture medium.

Preparations of the third component of human complement (C3) inhibit human lymphocyte blastogenic response to mitogens and antigens when cultured in serum-free medium or in medium supplemented with 5% autologous serum (AS). In contrast, when the culture medium was supplemented with 5% foetal calf serum (FCS), C3 failed to inhibit responses to mitogen (concanavalin A) or to antigen (streptolysin O); some FCS lots allowed stimulation rather than inhibition of the lymphocyte responses. Moreover, when lymphocytes were cultured in serum containing equal amounts of FCS and AS, no inhibition was seen. Our findings may explain previous studies which suggest that C3 enhances or has no effect on lymphocyte responses.

Antigens↗

PubMed1976

[Mesangiocapillary glomerulonephritis and rheumatoid arthritis. A case with diagnostic and therapeutic questions (author's transl)].

A 34 years old white male patient suffering from a seropositive "probable" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulnophritis. Rheumatoid factor-Latextest and Waaler-Rose-Titers and IgM have been found highly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within the normal range. The rapid progression of both diseases forced us to start an immunosuppressive drug therapy using azathioprine and steroids, 18 months after the beginning of the treatment the patient is well, has only slight proteinuria, normal levels of complement and no joint pain. The possible connections between rheumatoid arthritis and mesangiocapillary glomerulonephritis in this case as well as the therapeutic approaches are discussed.

Adult↗

PubMed1994

Developmentally regulated effects of lipopolysaccharide on biosynthesis of the third component of complement and factor B in human fibroblasts and monocytes.

Developmental regulation of the effects of lipopolysaccharide (LPS) on complement protein biosynthesis was studied in human fibroblasts from fetuses, newborn infants and adults, and in human monocytes from newborn infants and adults, using RNA blot analysis and immunoprecipitation of metabolically radiolabelled cell lysates. The responsiveness of the third component of complement (C3) and factor B protein synthesis to LPS is limited by translational mechanisms in the newborn infant and by pretranslational mechanisms in the fetus. Translation of RNA from LPS-induced cells in a rabbit reticulocyte lysate cell-free translating system indicated no differences in specific translational activity between LPS-induced adult and neonatal RNA, suggesting that LPS-induced neonatal C3 and factor B transcripts are translationally competent, but lack either access to relevant protein synthetic pathways or co-factor(s) necessary for translation. Interferon-gamma (IFN-gamma) enhanced translational activity of LPS-induced C3 and factor B transcripts in neonatal cells, suggesting that lack of translation in these cells may be due to the absence of a necessary co-factor. Experiments with LPS and cycloheximide or LPS and interleukin-1 alpha (IL-1 alpha) suggested that a newly synthesized protein did not participate in translational regulation and that LPS induction did not alter translational activity of IL-1 alpha-induced C3 and factor B transcripts. We conclude that the responsiveness of C3 and factor B protein synthesis to LPS is regulated at developmentally unique and specific steps in gene expression.

Adolescent↗