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PubMed1997

Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure.

Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects (P < 0.01). This defect persisted when zymosan opsonized by control serum was used (P < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects (P < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor.

Acetaminophen↗

PubMed1999

[Significance of the absorption of macromolecules for the immune response of an organism].

Numerous antigens are offered to the living organism by the daily food. With these investigations the influence of orally administered human gammaglobulin (HGG) on the immunity of sensitized animals after systemic immunization should be clarified. Experiments were performed in rabbits. Changes of the circulation were measured by bloodpressure registration and measurements of the organ flow. Simultaneous investigations of the antibody content, complement C3 and histamin were performed in the peripheral blood. In orally fed animals as well as in non fed controls an i.v. antigen challenge was performed. The level of circulating antibodies could be significantly decreased (60%) by the oral administration of HGG. In control animals the parenteral antigen challenge resulted in a mortality rate of 50%. In these animals the bloodpressure decreased significantly and long lasting, whereas antigen fed animals showed only a slight change in bloodpressure with normalization after a short period. During oral absorption of antigen complement factor C3 remained unchanged. In the first hour after the oral antigen administration a significant increase of histamin in the peripheral blood could be observed. Investigation with regard to the fate of the antibodies which were decreased by antigen feeding showed a storage in the layers of the gut which was depending on the dosage. It could be demonstrated that it is possible to influence the systemic immune response by the enteral application of macromolecules and this is also relevant for reactions of the circulation.

Animals↗

PubMed1993

Binding of bovine fibronectin to mastitis-causing Streptococcus agalactiae induces adherence to solid substrate but not phagocytosis by polymorphonuclear cells.

Streptococcus agalactiae is frequently associated with mastitis in cattle, and fibronectin is a host protein which interferes with infection, particularly at mucosal sites. The binding of bovine fibronectin to S. agalactiae was investigated by enzyme-linked immunosorbent assay (ELISA). Binding was time-dependent and dose-dependent. Most of the strains tested showed low ELISA activity, but some strains (six out of 17) had much higher activity. The highest-binding strains of S. agalactiae were able to adhere to bovine fibronectin-coated polystyrene. Adherence was inhibited by arginine or gelatin, but was slightly favored by soluble fibronectin. Fibronectin did not contribute to the opsonization (deposition of complement C3) and phagocytosis of the strain which bound the highest amount of fibronectin, even when polymorphonuclear cells were activated with serum-derived chemotaxin (C5a). These data suggest that fibronectin might promote tissue adherence but not phagocytosis of S. agalactiae in the mastitis process.

Animals↗

PubMed1982

The immunological state in chronic renal insufficiency.

To evaluate the immunological state in chronic renal insufficiency, the Authors studied cellular and humoral immunity in 292 patients with chronic renal failure. They were divided into 3 groups: 1) 37 with creatinine clearance between 50 and 20 ml/min; 2) 57 with creatinine clearance between 20 and 8 ml/min; 3) 178 treated by hemodialysis. In vivo and in vitro tests, that is DNCB, PPD skin tests, spontaneous, active and EAC rosettes, surface membrane immunoglobulin test, complement (C3, C4) and serum immunoglobulins were taken as markers of the immune response. Cell-mediated immunity was found to be significantly impaired in patients with terminal renal insufficiency or on hemodialysis and also markedly reduced in patients with non-terminal renal insufficiency. Humoral immunity produced less significant results: the B lymphocyte count and serum immunoglobulins were normal; only C3 levels were found below normal range. Thus it would seem that cell-mediated immunodeficiency appears in an early stage of chronic renal failure and that hemodialysis does not improve this deficiency.

Adult↗

PubMed1975

Association and linkage between alcoholism and eleven serological markers.

Sera from alcoholics and their nonalcoholic first-degree relatives were analyzed for 11 serological markers. A lower prevalence of the S antigen in the nonalcoholic relatives and linkage in repulsion between the D gene of the Rh system and alcoholism were found. All the alcoholics and the relatives had an SS phenotype, when analyzed for complement C3, compared with a prevalence rate of about 50% in other studies. The first two associations involve blood groups, the latter a serum protein.

ABO Blood-Group System↗

PubMed1977

Necrobiosis lipoidica. An immunofluorescence study.

Biopsy specimens from 12 patients with necrobiosis lipoidica (diabeticorum) were studied by direct immunofluorescent microscopy. The immunoglobulin IgM was present in blood vessel walls of involved skin from six patients, and the third component of complement (C3) was present in the blood vessel walls of involved skin from seven patients. The immunoglobulin IgA was similarly observed in two patients. In addition, IgM, C3, or fibrinogen were observed at the dermal-epidermal junction of involved skin from seven patients. Necrobiotic areas invariably contained fibrinogen. These findings suggest that an immunecomplex vasculitis may be involved in the pathogenesis of necrobiosis lipoidica.

Adolescent↗

PubMed1979

Immunopathologic studies of pneumonitis in systemic lupus erythematosus.

We performed immunohistopathologic studies on biopsied lung tissue obtained from two patients with lupus pneumonitis using immunofluorescence, immunoperoxidase, electron microscopy, and acid-microelution. In both patients, immunofluorescence showed granular deposits of IgG, the third component of complement (C3), and DNA in the alveolar walls. The immunoperoxidase technique in both and electron microscopy in one showed that these deposits were in the interstitium of the alveolar walls and in the alveolar capillary walls. The eluates obtained from cryostat sections of the biopsied lungs contained antinuclear factor of IgG class in one patient and showed anti-DNA antibody activity in both. We suggest that the deposits are immune complexes composed of DNA, anti-DNA antibody, and complement and that deposits of DNA-anti-DNA immune complex may play a role in lupus pneumonitis.

Adolescent↗

PubMed1997

[Effects of Staphylococcus aureus protein A on the production of primary host defense factors against S. aureus infection].

In vitro examination was carried out to investigate the effects of protein A of Staphylococcus aureus (S. aureus) on the production of fibronectin (Fn) and the third component of complement (C3) by macrophages and that of CD11b, CD49e and H2O2 by granulocytes. Fn production of cultured murine peritoneal macrophages (M phi ) increased significantly (P < 0.01) by treatment for 4 hr at 37 degrees C with recombinant PA (rPA) and the supernatant of overnight culture of S. aureus Cowan I strain (CoCS) (p < 0.01), not that of Wood 46 strain (WoCS), in comparison with that of control. The activity of rPA was inhibited strongly in the presence of CYH (1.0 microgram/ml). The production of C3 by cultured M phi did not increased by treatment for 4 hr at 37 degrees C with rPA, CoCS and WoCS. In these cells treated with CoCS and WoCS, however, the production increased by cultivation in serum free medium for a further 20 hr at 37 degrees C after the treatment. But increase was not found in rPA treated cells. On the other hand, the production of Mac-1, VLA-5 and H2O2 by granulocytes did not increase by treatment with rPA and CoCS. These results show that rPA and PA in CoCS are major components which stimulates Fn synthesis and secretion by cultured M phi some component(s) contained in the supernatant of overnight culture of S. aureus increased the production C3 by cultured M phi , and the supernatant may not contain stimulators to induce production of CD49e, CD11b and H2O2. Increase of Fn production of M phi by PA stimulation may play an important role in the primary host defense against S. aureus infection.

Animals↗

PubMed1982

Deposits of complement and immunoglobulins in vessel walls in pyoderma gangrenosum.

Previous immunofluorescence studies on pyoderma gangrenosum (PG) proved negative. Biopsies from the ulcer edge of 8 patients with PG were examined by immunofluorescence microscopy. Deposits of complement C3 were seen in the vessel walls of all samples, IgM in three and IgA in one. Granular deposits of C3 were seen at the dermal--epidermal junction in 2 patients. Biopsies from clinically normal skin of 6 of the patients were negative. It is suggested that deposition of immune complexes in the dermal vessel walls may play a role in the pathogenesis of PG.

Blood Vessels↗

PubMed1979

Study on the turnover of the receptor for the third component of complement on human lymphoid cells.

The in vitro turnover of the receptor for the third component of complement (C3) was studied in normal peripheral blood lymphocytes (PBL) and in lymphoblastoid cells from established cell cultures of both "normal" and "malignant" origin. The turnover was evaluated by studying i) the disappearance rate of the C3-receptor in cells in which the protein synthesis was blocked by cycloheximide and puromycin, ii) the reexpression rate of the C3-receptor after treatment of the cells with either rabbit antiserum against B lymphocytes or mouse C activated through the alternative pathway by inulin. The results show that the C3-receptor of all the lymphoid cells has roughly a half-life of about 3 to 4 hr. However, the cultured lymphoblastoid cells were less sensitive than normal PBL to inhibition by cycloheximide and showed a faster reexpression rate of the C3-receptor. A spontaneous release of the receptor was found to occur, since a receptor-like activity was detected in the spent culture medium of long-term cultured lymphoid cells.

Animals↗

PubMed1999

[Complement and serum immunoglobulins in homozygous and heterozygous sickle cell anemia in Senegal].

Sickle cell disease is an hereditary hemoglobinopathy syndrome which provokes deglobulization crisis and infectious complications. These infectious diseases may be due to a permanent activation of the immune system. The aim of our study was to explore alternative pathway by measuring C3 complement and the classical pathway by C4 complement. The level of immunoglobulins IgA, IgG and IgM was also measured in the subjects sera. Thirty homozygous sickle cell anemia (SS), 25 heterozygous (AS) and 34 controls subjects (AA) were recruited in the Hôpital d'Enfants Albert Royer (HEAR), Fann hospital and Centre National de Transfusion Sanguine (CNTS). Radial Immunodiffusion (RID) technics using specific antisera for C3c, C4c, IgA, IgG and IgM were used in our study. Homozygous SS proved an increase level of IgA (50%, p < 0.003) and IgG (47%, p < 0.003), unlike of IgM level. The C3c complement decrease significantly in (27%) of homozygous SS patients (p < 0.0005) unlike of C4c level. This low level of C3 and IgG in sickle cell homozygous patients can explain the higher susceptibility to infection in these patients. Normal level of C4 and low level of C3 show activation of alternative pathway. Heterozygous AS showed a normal level of C4, C3 and immunoglobulins. Our results suggests a direct involvement of the complement system in sickle cell disease and the depletion of C3 registered was a possible cause of increased susceptibility to infections in patients with homozygous sickle cell anemia.

Adolescent↗

PubMed1996

Human peripheral blood lymphocyte-reconstituted, severe combined immunodeficient mice as a model for porcine islet xenograft rejection in humans.

Previously we established human peripheral blood lymphocyte-reconstituted severe combined immunodeficiency (SCID) (hu-PBL-SCID) mice as a model for human islet allograft rejection. The function of xenografted hu-PBL was confirmed to reject human alloislets in hu-PBL-SCID mice. In this study, we modified this model as a porcine islet xenograft to study porcine islet rejection in humans. Chimeric mice were used as the recipients of porcine islets to reveal the mechanisms of xenograft rejection in humans. SCID mice were reconstituted with 30 x 10(6) of hu-PBL initially, and 10 x 10(6) of antihuman CD3-primed PBL was injected intraperitoneally 2 days later as a booster. An additional booster injection provided greater possibility (86.7%, n = 15) of chimera establishment as well as a higher human immunoglobulin concentration in SCID mice than the single injection group. In an in vitro assay, sera from hu-PBL-SCID mice were found to recognize porcine islets by FACS staining. In an in vivo study, immunofluorescent analysis of a frozen section showed that human immunoglobulins adhered to the xenografted porcine islet under the kidney capsule of hu-PBL-SCID mice. Although no mouse immunoglobulins were detected on sections, mouse complement (C3) was shown to adhere to the xenografted porcine islet. Thus, hu-PBL-SCID mice provide a useful model for investigating the real-life situation of porcine islet xenograft rejection in humans.

Animals↗

PubMed1994

Effect of serum from HIV-infected subjects on superoxide production by polymorphonuclear neutrophils.

Superoxide (O2.-) production by polymorphonuclear neutrophils (PMN) was assessed in 17 subjects with asymptomatic infection (AI), 16 patients with acquired immunodeficiency syndrome (AIDS), and 12 healthy normal subjects. The effect of patients' serum on the oxidative activity of normal and patients' PMN was also investigated. The O2.- production, nonstimulated and stimulated with zymosan particles in the presence of normal serum, was similar to that of normal controls in both groups of patients. The serum from 11 out of the 17 AI subjects (65%) induced an increase in the stimulated O2.- production in normal and patients' PMN, while the serum from 8 out of the 16 AIDS patients (50%) induced a diminution. These effects did not appear to be related to complement C3 and circulating immune complex levels, but suggest that PMN of HIV-seropositive patients do not present an intrinsic dysfunction and that the impact of serum factor(s) affects the normal oxidative activity of these cells depending on the stage of infection.

Acquired Immunodeficiency Syndrome↗

PubMed1984

Serum MBP immunoreactivity and immunoglobulin level as markers of tumour type.

Forty three patients, admitted to the department of Neurological Surgery for management of central nervous system tumours, were studied pre-operatively for serum myelin basic protein immunoreactivity as a marker of central nervous system lesion and for circulating immunoglobulins and complement (C3) levels. Myelin basic protein concentration did not appear to correlate with tumour type or grade. Serum immunoglobulin levels were found to be within the normal range but the mean IgM level was significantly higher in the glioma group when compared with meningiomas.

Adult↗

PubMed1991

[The significance of the heparin precipitable fraction in lung diseases].

The authors recently experienced a case of idiopathic interstitial pneumonia (IIP) that exhibited skin ulcers due to increased heparin precipitable fraction (HPF) in plasma. This case prompted us to investigate the occurrence and significance of HPF in interstitial pneumonia (IP). The subjects included patients with IIP (acute exacerbation 6 cases, chronic active stage 12 cases), IP associated with collagen vascular disease (CVD) (9 cases) and granulomatous lung diseases (7 cases). The data indicated that all of the cases with acute exacerbation of IIP exhibited increased plasma HPF values (218-951 mg/dl) compared to those of normal controls (less than 180 mg/dl). In contrast, the values ranged within normal limits in all of the cases with IP associated with CVD. In a companion study, we measured plasma HPF values in patients with lung cancer, bacterial pneumonia and diffuse panbronchiolitis. It was found that 22% of the subjects showed increased plasma HPF values. We also investigated whether there were correlations between plasma HPF and various inflammatory parameters. The data revealed that there were correlations between HPF and ESR, CRP, alpha 1-globulin, alpha 2-globulin, complement (C3) or fibrinogen. However, there was no correlation between HPF and fibronection. These results suggest that plasma HPF is valuable to evaluate the acute exacerbation of IIP, although the elevation of plasma HPF levels is not specific.

Acute-Phase Reaction↗

PubMed1990

Structural homologies of component C5 of human complement with components C3 and C4 by neutron scattering.

The complement component C5 is one of a family of structurally related plasma proteins that includes components C3 and C4. Activation of C5 is the initial step in the formation of the membrane attack complex of complement. Analysis of the solution structure of C5 and comparisons with similar analyses of the structures of C3 and C4 are reported here. Neutron solution scattering gave an Mr for C5 of 201,000, which demonstrates that C5 is monomeric in solution. The radius of gyration RG of C5 at infinite contrast is 4.87 nm and corresponds to an elongated structure. The longest length of C5 was determined to be at least 15-16 nm from three calculations on the basis of the RG, the scattering intensity at zero angle I(0), and the indirect transformation of the scattering curve into real space. Comparison of the RG and contrast variation data and indirect transformations of the scattering curves for C3, C4, and C5 show that these have very similar structures. Comparisons of the C5 scattering curve with Debye small-sphere models previously employed for C4 and C3 show that good curve fits could be obtained. Unlike previous studies that have suggested significant differences, these experiments indicate that, while C5 differs from C3 and C4 in its activation and inactivation pathways, significant structural homology exists between the native proteins, as might be predicted from their high (and similar) sequence homology.

Complement C3↗

PubMed2002

Different associations of C-reactive protein, fibrinogen and C3 with traditional risk factors in middle-aged men.

BACKGROUND: Some acute phase proteins are associated with both ischemic events and traditional risk factors. Since they are strongly interrelated, each of them partly reflects the characteristics of other proteins. This study was carried out to ascertain the specific preferential associations of some acute phase proteins with traditional risk factors for atherosclerotic disease. METHODS: High-sensitivity C-reactive protein, fibrinogen and C3-complement were assessed in 288 unselected men aged 55-64 years. Three multiple linear regression analyses were performed, in which each of the three acute phase proteins was considered the dependent variable of both traditional risk factors and the other two proteins. RESULTS: The three acute phase proteins strongly correlated with each other. Moreover, C-reactive protein was independently associated with triglycerides (P<0.0001), age (P=0.0130), body mass index (P=0.0179), and acute (P=0.0280) and chronic (P=0.0582) inflammations (R2=0.17). Fibrinogen was associated with alcohol consumption (inversely, P=0.0001) and smoking (P=0.0598) (R2=0.06). Finally, C3 was associated with insulin (P<0.0001), cholesterol (P=0.0001), sedentarity (P=0.0028), glucose (P=0.0077), and systolic blood pressure (P=0.0124) (R2=0.28). CONCLUSIONS: When simultaneously studied in multivariate analysis, acute phase proteins have different preferential associations with traditional risk factors, a probable consequence of their involvement in different cellular activations and metabolic processes.

Age Factors↗

PubMed1975

The control of serum protein synthesis in hepatoma-fibroblast hybrids.

Hybrids between mouse hepatoma cells (which secrete several serum proteins) and mouse or rat fibroblasts (which do not secrete these proteins) produce transferrin and the third component of complement (C3) like the parental hepatoma cells, while they do not secrete either albumin or alpha-fetoprotein (AFP). This lack of albumin and AFP secretion is probably due to a lack of synthesis, rather than to a simple defect in secretion. The cessation of albumin and AFP production is not dependent upon the parental fibroblast nor upon the selection conditions; it is best explained by a shut-off synthesis and could thus reflect the existence of a regulatory mechanism. This would imply a difference between the control of albumin and AFP synthesis and that of transferrin and C3 synthesis. On the other hand, in agreement with Peterson and Weiss (1972), hybrids between rat hepatoma cells and mouse fibroblasts continue to product rat albumin. This suggests that the mouse hepatoma cells differ from the rat hepatoma cells in the way they control albumin production.

Animals↗