Biomedical subjects

K Høgåsen

Publications and source records attributed to K Høgåsen.

At least 19 recordsLinked to original sources

PubMed2001

Increased systemic activation of neutrophils but not complement in preeclampsia.

OBJECTIVE: To investigate whether neutrophils and systemic complement are activated in pregnancies complicated by preeclampsia more than in normal pregnancies. METHODS: We measured native complement components and activation products in plasma by enzyme immunoassays in 19 women with uncomplicated pregnancies, 15 with preeclampsia before cesarean deliveries, and 16 nonpregnant women. Neutrophil activation was measured by specific enzyme immunoassays for myeloperoxidase and lactoferrin. RESULTS: Myeloperoxidase was significantly higher in women with preeclampsia (197 microg/L, 95% confidence interval [CI] 94, 646) than in women with uncomplicated pregnancies (124 microg/L, 95% CI 70, 289; P =.009), whereas lactoferrin did not differ between groups. C4 was decreased in preeclamptic women (0.16 g/L, 95% CI 0.07, 0.48) compared with women with uncomplicated pregnancies (0.21, 95% CI 0.10, 0.30, P <.001). There were no differences for the other native complement components. There was a significant decrease in C1rs-C1 inhibitor, 13 AU/mL (95% CI 9, 34) versus 19 (95% CI 13, 38) (P < or =.001) in normal pregnant women compared with nonpregnant women. There also was an increase in C3, C4, C9 (data not shown), C4bp, 132% (95% CI 94%, 161%) versus 91% (95% CI 57%, 128%); C3bc (7.4 AU/mL, 95% CI 4.2, 10.7) versus 4.8 AU/mL (95% CI 3.2, 7.3) and C4bc (8.6 AU/mL, 95% CI 5.7, 14.0) versus 3.5 AU/mL (95% CI 2.2, 6.7) in normal pregnant women compared with nonpregnant women (P < or =.001). CONCLUSION: Neutrophil activation in preeclampsia was shown by systemic increases in myeloperoxidase. Except for a decrease in C4, systemic complement activation could not be detected in preeclampsia.

Adult↗

PubMed2001

Complement activation directly induced by Helicobacter pylori.

BACKGROUND AND AIMS: Helicobacter pylori is a frequent gram-negative colonizer of the human stomach. Its interaction with complement may be involved in the pathogenesis of chronic gastritis, and was mechanistically studied in vitro. METHODS: Four H. pylori strains, 2 cytotoxin-associated genes (cag)A+ and 2 cagA-, were isolated from infected patients. Bacteria or purified H. pylori lipopolysaccharides (LPSs) were incubated with nonimmune serum at 37 degrees C; the activation products C3b/iC3b/C3c (C3bc) and terminal complement complex (TCC) were then quantified by immunoassays. The serum sensitivity of 1 strain (L01, cagA+) was tested by counting the numbers of colony-forming units. RESULTS: All strains and LPSs generated large amounts of C3bc and TCC. Blocking of the classic complement pathway by the calcium chelator ethylene glycol tetraacetic acid (EGTA) markedly reduced the complement products, suggesting that H. pylori and its LPSs directly engage the classic activation pathway. H. pylori was shown to be serum sensitive, but 30% or more nonimmune serum was necessary to induce marked killing. After 5 minutes, swelled bacteria coated with C3bc and TCC were shown. CONCLUSIONS: H. pylori is complement sensitive and activates the classic pathway even in the absence of specific antibodies. Released cell wall constituents such as LPSs can activate complement and may explain why this bacterium induces gastric pathology without invading the mucosa.

Antibodies, Bacterial↗

PubMed2000

Interaction between human complement and a pectin type polysaccharide fraction, PMII, from the leaves of Plantago major L.

The interaction between a pectin type polysaccharide fraction, PMII, isolated from the leaves of Plantago major, and human complement was tested in two different hemolytic complement-fixation tests and in addition by two ELISA methods detecting complement-activation products. Sera were used as a complement source of 10 arbitrary human volunteers, individually and as a pool. The complement-fixation tests were designed to measure the concentration of the pectin necessary to inhibit 50% of the hemolysis (ICH(50)). The ELISA tests for complement-activation products were measured in AU/mg using a fully activated serum as a standard. We observed a more than 200-fold difference in ICH(50) activity of the PMII pectin in one of the hemolytic tests by varying the individual sera used as complement-source. On the other hand, the ELISA complement-activation tests showed no significant variation in activity of the PMII depending on the complement-serum used. The level of antibodies against PMII detected in the complement-sera did not correlate with the ICH(50) activity of PMII. The results show that PMII is a potent complement activator with an activity of the same order of magnitude on a weight basis as that of aggregated human immunoglobulin (Ig)G. This activation leads to a complement consumption probably explaining the PMII's effect in the complement-fixation tests. PMII seems to be an activator both on the classical and the alternative pathway of activation. The results might be related to the reported wound-healing effect of the leaves of Plantago major.

Adult↗

PubMed2000

The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency.

Native complement factors and complement activation products were measured in healthy neonates (n = 72) and in a group of infants with premature prolonged rupture of the membranes (PPROM) without sepsis (n = 10). Vitronectin concentration in normal cord blood was not correlated with gestational age, and the median value was 86.0% of adult values. This was markedly higher than other native complement factors studied (factor B: 35.9%, C4: 45.1%, C3: 56.2%). The concentration of C9 showed a positive correlation with gestational age and was very low, 10.8% of normal adult values in cord blood and 8.3% in the patients. Fifteen percent of the neonates had C9 levels lower than 2% of adult values. The complement activation products Bb and SC5 b-9 were significantly elevated in the patients (159% and 130% of control values, respectively), indicating alternative and terminal pathway activation. In contrast, C4 bc and C3 bc levels were not increased. The maximum amount of SC5 b-9 which could be generated in the neonatal sera by cobra venom factor was highly correlated with C9 concentration (rs = 0.86, p = 0.0001) The profound C9 deficiency found in neonates is correlated with gestational age, limits the capacity to form bacteriolytic C5 b-9 (m) and may predispose for severe invasive bacterial infection. The plasma level of SC5 b-9 under normal conditions was very low, only 0.3% (0.1%-3.0%) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels.

Bacteremia↗

PubMed1999

Compstatin, a peptide inhibitor of C3, prolongs survival of ex vivo perfused pig xenografts.

Compstatin, a newly described C3-binding peptide, inhibits complement activation by blocking C3 convertase-mediated cleavage of C3. As the complement activation is an essential part of the rejection reaction, we evaluated the ability of Compstatin to delay or prevent hyperacute rejection in an ex vivo xenograft model. Pig kidneys were perfused with fresh human blood containing either Compstatin (n=6) or a control agent (n=6). Graft survival and activation of complement, leukocytes and platelets both in the fluid-phase and in the tissue were examined. The survival of the Compstatin-perfused kidneys (median, 380 min) was significantly (P=0.0036) longer than that of the controls (median, 90 min). The classical complement pathway (C1rs-C1inhibitor and C4bc) was significantly and equally activated in both groups during the first 60 min. C3 activation products increased fivefold and terminal complement complex eightfold in the control group, but no increase occurred in the Compstatin group during this period. Immunohistochemistry showed less C3 and fibrin deposition and immune electron microscopy showed less terminal SC5b-9 complement complex deposition in the Compstatin group. A significant change in total white cells, neutrophils, myeloperoxidase, and expression of the surface activation markers CD11b (CR3) and CD35 (CR1) and CD62L (L-selectin) was observed in both groups. Leukocyte activation was lower in the Compstatin group but the difference was not statistically significant. There were no differences in platelet counts, thrombospondin, soluble P-selectin or beta-thromboglobulin between the groups. We conclude that Compstatin prolongs graft survival and suggest that it may be a useful agent for attenuating hyperacute rejection by inhibiting C3 and thus terminal complement pathway activation.

Animals↗

PubMed1998

Effect of soluble complement receptor type 1 on reperfusion edema and neutrophil migration after lung allotransplantation in swine.

OBJECTIVE: Soluble complement receptor type 1 inhibits complement activation by blocking C3 and C5 convertases of the classical and alternative pathways. We evaluated the effect of soluble complement receptor type 1 on lung allograft reperfusion injury. METHODS: Left lung transplantation was performed in 13 weight-matched pigs (25 to 31 kg) after prolonged preservation (20 hours at 1 degree C). One hour after reperfusion the recipient contralateral right lung was excluded to assess graft function only. Complement activity and C3a levels were measured after reperfusion and at the end of the assessment. Extravascular lung water index, intrathoracic blood volume, and cardiac output were assessed during a 5-hour observation period. Gas exchange and hemodynamics were monitored. At the end of the 5-hour assessment period, myeloperoxidase assay and bronchoalveolar lavage were performed to assess neutrophil migration, and C5b-9 (membrane attack complex) deposits in the allograft were detected by immunohistochemistry. Two groups were studied. In group II (n = 6) recipient animals were treated with soluble complement receptor type 1 (15 mg/kg) 15 minutes before reperfusion. Group I (n = 7) served as the control group. RESULTS: Serum complement activity was completely inhibited in group II. In contrast to group I, C5b-9 complexes were not detected in group II allograft tissue samples. C3a was reduced to normal levels in group II (p = 0.00005). Extravascular lung water index was higher in group I animals throughout the assessment period (p = 0.035). No significant difference in allograft myeloperoxidase activity (p = 0.10) and polymorphonuclear leukocyte count of the bronchoalveolar lavage fluid (p = 0.057) was detected. CONCLUSION: Inhibition of the complement system by soluble complement receptor type 1 blocks local complement activation in the allograft and reduces posttransplantation reperfusion edema but does not improve hemodynamic parameters.

Animals↗

PubMed1998

High-dose intravenous immunoglobulin treatment activates complement in vivo.

Several complement modulating effects of high-dose intravenous immunoglobulins (IVIG) have been proposed from in vitro studies and experimental animal models. However, the in vivo effects of IVIG on plasma complement in humans are yet not known. We have investigated the in vivo effects of IVIG on complement in seven women with unexplained recurrent spontaneous abortion who were without evidence of autoimmune disease. Samples were obtained before and after the very first infusion of IVIG. There was a marked increase in immunoglobulin G (IgG) from (median and range) 12.4 (9.4-15.9) to 26.8 (22.4-30.0) g/l but no change in immunoglobulin A (IgA) or immunoglobulin M (IgM). A significantly increased complement activation was demonstrated using neoepitope-specific enzyme immunoassays to the activation products C3bc (median increased from 9.8 to 31.2 AU/ml), Bb (0.66-1.66 g/ml), C5a (10.5-12.7 ng/ml), and TCC (0.81-2.19 AU/ml) (P = 0.015 for all). There were no changes in antigenic concentrations of individual complement components or regulators (C1q, C4, C3, C1-inhibitor, C4b-binding protein) and no decrease in complement haemolytic activity (classical and alternative CH50), which were all within the normal range. The classical pathway activation products C1rs/C1-inhibitor complexes, C4bc and C4d were elevated in all patients before IVIG treatment and did not change significantly during treatment. In conclusion, IVIG induced a significant activation of complement in vivo.

Abortion, Habitual↗

PubMed1998

Characterization of soluble terminal complement complex assembled in C8beta-deficient plasma and serum.

Sera genetically deficient in either the alpha-gamma or the beta-subunit of complement component C8 virtually lack haemolytic activity. We have studied the formation and the structural organization of the soluble terminal complement complex (TCC) assembled in these sera following activation with cobra venom factor (CVF). The TCC concentration in the activated C8alpha-gamma and C8beta-deficient samples was 0.2% and 4%, respectively, when compared with zymosan-activated normal serum. TCC was purified from the activated C8beta-deficient samples by affinity chromatography and analysed by immunoblotting and enzyme immunoassay. No C8beta was detected in one TCC preparation, while 7% of the normal level was present in the other. The level of the other terminal components, including that of C8alpha-gamma, was normal. The ability of C8alpha-gamma to promote the assembly of TCC in the presence of a limited amount of C8beta or in the apparent absence of this subunit was confirmed using purified components, by mixing C5b6 and either of the purified C8 subunits together with C7 and C9. These data show that soluble TCC can be formed in C8beta-deficient sera that contain little or no C8beta.

Complement C5↗

PubMed1998

In situ complement activation in porcine membranoproliferative glomerulonephritis type II.

Pigs genetically deficient in complement factor H all develop lethal membranoproliferative glomerulonephritis (MPGN) type II characterized by massive glomerular deposits of complement, intramembranous dense deposits, and mesangial hypercellularity. To elucidate the chronological relationship between these glomerular changes, and to precisely determine the localization of glomerular complement deposits, we studied kidney specimens from factor H-deficient piglets at different ages from fetal life until terminal kidney failure had developed. Deposits of C3 and the terminal complement complex localized within the glomerular basement membrane (GBM) were present already in factor H-deficient fetuses, without concurrent intramembranous dense deposits or mesangial hypercellularity. Incipient subendothelial dense deposits containing complement appeared no earlier than four days after birth, and intramembranous dense deposits in older piglets with established MPGN type II also contained large amounts of complement as detected by immune electron microscopy. Onset of kidney failure coincided with pronounced mesangial hypercellularity and expansion, compromising glomerular capillary patency. Formation of glomerular capillary wall double contours coincided with electron microscopic evidence of laminar disintegration of intramembranous dense deposits. Complement was also deposited in the mesangial matrix, but not on glomerular cells. We conclude that all components of the alternative and terminal pathways of complement have access into the GBM and the mesangial matrix. In the absence of factor H, complement is spontaneously activated and deposited in situ in these locations resulting in dense deposit formation. It is proposed that factor H dysfunction may play an essential role even in human MPGN type II.

Animals↗

PubMed1998

Effect of filtration and storage of platelet concentrates on the production of the chemotaxins C5a, interleukin 8, tumor necrosis factor alpha, and leukotriene B4.

BACKGROUND: The production in platelet concentrates (PCs) of C3 activation products (C3bc), terminal complement complex (TCC), and chemotaxins C5a, interleukin (IL)-8, tumor necrosis factor alpha (TNFalpha), and leukotriene B4 (LTB4) and the proposed reduction in concentration of the chemotaxins by white cell reduction were examined. STUDY DESIGN AND METHODS: Samples were collected from supernatants of PCs produced by apheresis (apheresis PCs) or from buffy coats (BC PCs) immediately after the production, after white cell-reduction filtration on Day 1, and after 5-day storage, and examined by enzyme immunoassays. RESULTS: Complement was activated in all PCs during storage, and the concentration of activation products was not influenced by prestorage filtration. In prestorage white cell-reduced BC PCs, only C3bc levels increased. Levels of IL-8, TNFalpha, and LTB4 increased during storage of apheresis PCs, but not in filtered units, except for LTB4. In contrast, levels of IL-8 decreased after storage of filtered BC PCs. C5a correlated significantly with IL-8, which also correlated with TNFalpha and LTB4. CONCLUSION: Both C5a and TNFalpha generation in apheresis PCs seem to induce white cell IL-8 production, which mediates cellular LTB4 release. Prestorage white cell reduction is recommended for reducing chemotactic cytokine and leukotriene levels in all PCs. Production of BC PCs is recommended to achieve less complement activation, which is not affected by filtration.

Blood Platelets↗

PubMed1998

Involvement of antilipoarabinomannan antibodies in classical complement activation in tuberculosis.

We examined alternative and classical complement activation induced by whole bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculosis products. After exposure to BCG, there were higher levels of the terminal complement complex in sera from Indian tuberculosis patients than in sera from healthy controls. The addition of BCG with or without EGTA to these sera indicated that approximately 70 to 85% of the total levels of the terminal complement complex was formed by classical activation. Sera from Indian tuberculosis patients contained more antibody to lipoarabinomannan (LAM) than sera from healthy Indians. Levels of anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated positively with classical activation induced by BCG in the sera. By flow cytometry, deposition of C3 and terminal complement complex on bacilli incubated with normal human serum was demonstrated. The anticomplement staining was significantly reduced in the presence of EGTA and EDTA. Flow cytometry also revealed the binding of complement to BCG incubated with rabbit anti-LAM and then with factor B-depleted serum. This indicates that classical activation plays a major role in complement activation induced by mycobacteria and that anti-LAM IgG on the bacilli can mediate this response. Classical complement activation may be important for the extent of phagocytosis of M. tuberculosis by mononuclear phagocytes, which may influence the course after infection.

Adolescent↗

PubMed1997

Eradication of porcine factor H deficiency in Norway.

In pigs a hereditary deficiency of the complement-inhibitory protein factor H consistently leads to the development of lethal membranoproliferative glomerulonephritis type II. This autosomal recessive disease has been a common cause of early losses of piglets in the Norwegian Yorkshire breed, but has not been reported in the Norwegian Landrace breed. The aim of the present work was to identify carriers of factor H deficiency and to eradicate the disease from commercial pig populations. Factor H in plasma was measured by an enzyme immunoassay. Sixteen known carriers of the disease (parents of factor H-deficient offspring) had half the level of factor H (median 110, range 87 to 156 mg/litre) recorded in 17 homozygous healthy Yorkshire pigs (median 212, range 183 to 293 mg/litre) and 20 Landrace pigs (median 227, range 200 to 255 mg/litre). Factor H analysis in 397 piglets produced by the mating of known carriers revealed an approximately 1:2:1 distribution of individuals with very low, half-normal and normal levels of factor H representing homozygous deficient, heterozygous and homozygous healthy individuals. Thus, carriers could be identified reliably by measuring the plasma concentration of factor H. Most of the population of Norwegian Yorkshire breeding pigs (490 pigs) was therefore examined, and a half-normal factor H level consistent with the carrier state was found in 13.5 per cent. These animals were prevented from breeding and since then no losses of piglets suspected of being due to factor H deficiency have been reported. No carrier was identified among 102 Norwegian Landrace boars, almost excluding the existence of factor H deficiency in this breed.

Aging↗

PubMed1997

Infection with human cytomegalovirus (HCMV) stimulates monocyte production of complement factor 3.

Complement biosynthesis in monocytes is stimulated by different microorganisms including Gram negative bacteria and yeasts. We have tested the effect of human cytomegalovirus (HCMV) on complement factor 3 (C3) production by cultured human monocytes. The monocytes were challenged with either a crude or a purified HCMV preparation obtained from the supernatant of HCMV-infected fibroblasts. When the monocytes were infected with 2 pfu/cell of virus and cultured for 2 days, the increase in C3 production compared to control ranged from 3% to 162%, median 62% (p < 0.01). However, crude HCMV was even more potent in stimulating C3 production, as the increase in C3 values ranged from 104% to 507%, median 247% (p = 0.001). This indicates the presence in the crude HCMV preparation of a substance which acts synergistically with HCMV on the C3 production. When monocytes were stimulated by lipopolysaccharide (LPS), a well known inducer of C3, infection with crude or purified HCMV did not further increase C3 production. Both HCMV and substances produced during the propagation of HCMV in fibroblasts are able to stimulate C3 production in monocytes. Complement production by inflammatory cells may be of importance in host resistance against viral infections.

Cell Line↗

PubMed1997

Attenuation of changes in leukocyte surface markers and complement activation with heparin-coated cardiopulmonary bypass.

BACKGROUND: The inflammatory response induced by cardiopulmonary bypass can result in severe organ dysfunction in some patients. This postperfusion response is caused mainly by contact between blood and the foreign surface of the cardiopulmonary bypass equipment and includes adhesion of leukocytes to vascular endothelium, which precedes a series of events that mediate inflammatory damage to tissues. METHODS: Low-risk patients accepted for coronary artery bypass grafting were randomized to operation with the cardiopulmonary bypass surface either completely heparin coated (Duraflo II) or uncoated. There were 12 patients in each group. Blood plasma sampled during cardiopulmonary bypass was analyzed for complement activation (C3bc and terminal SC5b-9 complement complex) and neutrophil activation (lactoferrin and myeloperoxidase). In addition, neutrophils, monocytes, and platelets were counted, and the expression of surface markers on the neutrophils and monocytes (complement receptor [CR] 1, CR3, CR4, and L-selectin) and on the platelets (P-selectin and CD41) was quantified with flow cytometry. RESULTS: Clinical and surgical results were similar in both groups. In the group with the heparin-coated surface, the formation of the terminal SC5b-9 complement complex was significantly reduced, and the counts of circulating leukocytes and platelets were significantly less reduced initially but were higher at the end of cardiopulmonary bypass compared with baseline. Also, the expression of CR1, CR3, and CR4 was significantly less upregulated and the L-selectin, significantly less downregulated on monocytes and neutrophils. CONCLUSIONS: We conclude that heparin coating reduces complement activation and attenuates the leukocyte integrin and selectin response that occurs when uncoated circuits are used.

Antigens, Surface↗

PubMed1997

Effect of whole and fractionated intravenous immunoglobulin on complement in vitro.

Intravenous immunoglobulins (IVIG) are increasingly used for treatment of inflammatory diseases, and the modulation of complement may contribute to some of its beneficial effects. IVIG may bind C1q and activated C3 and C4, and enhance inactivation of C3b. We have previously shown that IVIG inhibited complement-mediated lysis solely via its Fc part through interaction with the classical pathway. In the present study we have investigated whole IVIG (Octagam, and Sandoglobulin) and the monomer, dimer and multimer fractions of Octagam with respect to complement activation in serum and inhibition of complement lysis of red cells. The isolated fractions were found to be stable, homogeneous (monomer, dimer or multimer) and pure (virtually only IgG). Both whole IVIG and its fractions significantly activated complement in serum and inhibited hemolysis compared with human albumin. These effects were most pronounced in the monomer, less in the multimer and least in the dimer fraction. The complement activation was shown to be mediated through the classical pathway since formation of C1rs-C1inh complexes and C4bc were increased, in contrast to Bb. Surprisingly, heat aggregation of Octagam was not followed by a corresponding increase in complement activation, as would be expected, unless it was dialysed before heating, suggesting that it is stabilized to avoid excess activation. In conclusion, the results support the hypothesis that IVIG causes a mild activation of complement in vitro. We suggest that this effect may contribute to the complement inhibitory properties of IVIG by diverting complement deposition from the target to the fluid phase.

Animals↗

PubMed1997

Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co-cultured agarose beads.

Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co-cultured agarose beads. Clusterin is a multifunctional regulatory protein rendering the terminal complement complex (TCC) soluble and unable to insert into cell membranes. The aim of the present study was to examine whether clusterin was an integral part of serum-derived TCC bound to agarose beads which activate the alternative pathway of complement. Further, we searched for evidence of clusterin synthesis in human umbilical vein endothelial cells (EC) and whether this synthesis was regulated by various proinflammatory cytokines (IL-1, IL-6, and TNF) and IFN-gamma. The clusterin and TCC on co-incubated beads were measured by radioimmunoassay based on primary anti-complement antibodies (anti-C3c, anti-TCC, anti-clusterin). We found that clusterin in serum experiments is bound to C9 in agarose bound TCC and not directly to the agarose. Addition of the protein synthesis inhibitor cycloheximide to cultured human umbilical vein cells resulted in a strong reduction (about 70%) of anti-clusterin binding to co-cultured beads, which strongly supports de novo synthesis of clusterin in EC. The results indicate that clusterin derived from the EC is linked with the TCC on the co-incubated beads for the following reasons: First, in serum experiments clusterin like vitronectin, was co-deposited with C9 in agarose-bound TCC. Second, cytokine stimulation of the EC with proinflammatory cytokines such as IL-1, IL-6 and TNF, known to increase the detection of bound TCC, also increased the amount of clusterin detected on the beads. Third, IFN-gamma, which reduces the concentration of bound TCC, exhibited the same effect on the amount of clusterin detected on such beads. There was a strong and dose-dependent reduction of anti-TCC binding from about 45% to about 95% when clusterin (5-40 micrograms/ml) was added to EC cultures. This effect was also evident (about 40-50% inhibition of bound TCC) using human serum as complement source. These results are probably mainly caused by clusterin binding to C5b-7, making this complex soluble without the capacity to bind to the agarose surface. This study supports the view that clusterin is a potent regulator of TCC at the levels of C5b-7 and C9.

Cells, Cultured↗

PubMed1997

Acquired C3 deficiency in patients with alcoholic cirrhosis predisposes to infection and increased mortality.

BACKGROUND: Acquired deficiencies of certain complement proteins and impaired opsonisation activity have been implicated in the pathogenesis of the increased susceptibility to infections of patients with alcoholic cirrhosis. METHODS: Serum concentrations of C3 and C4, plasma concentrations of C3bc, C9, and the terminal C5b-9 complement complex (TCC), and haemolytic complement activity (classic and alternative pathway) of serum, and serum opsonic activity were determined in 46 patients with compensated alcoholic cirrhosis, 31 who were decompensated, and in 15 healthy subjects. After 19 months (median) the investigated variables were analysed for their use in prognosis of recurrent infections and survival. RESULTS: C3 and C4 concentrations and the haemolytic complement activity of the alternative pathway were decreased in decompensated cirrhotic patients compared with controls (p < 0.01). Univariate analysis (log rank test) showed that low concentrations (< or = lower quartile) of C3 (p < 0.001) and C3bc (p < 0.05), haemolytic complement activity of the alternative pathway (p < 0.01) and classic pathway (p < 0.05), and decompensated cirrhosis (p < 0.001) were associated with an increased risk of infection and increased mortality. Multivariate (Cox) analysis showed that low C3 concentrations and decompensation of cirrhosis were significant predictors of infections and mortality (p < 0.02). CONCLUSIONS: Low serum C3 concentrations and decreased haemolytic complement function predisposes to infection and increased mortality in patients with alcoholic cirrhosis.

Adult↗

PubMed1996

Adhesion molecule expression and complement activation in vessel walls in synovial tissue from patients with chronic inflammatory joint disease.

Histopathology demonstrating a manifest vasculitis is a rare event in synovial tissue (ST) from patients with chronic inflammatory joint disease. As a possibly more subtle sign of a vasculitic process, complement activation in vessels in ST was studied. In the same tissues, the expression of the adhesion molecules ICAM-1 and E-selectin in vessel walls was examined, to see if the expression was related to vasculitic processes. The study was performed by use of direct immunofluorescence technique on cryostat sections of ST, using mouse monoclonal antibodies to the terminal complement complex (TCC, C5b-9), ICAM-1 and E-selectin. Expression of ICAM-1 was found in the vessel walls in all of 28 tissues tested, whereas E-selectin was found in 4 cases and TCC in 11. E-selectin and TCC were found together in only 1 tissue. The study supports the view that ICAM-1 is always, or nearly always, present in vessel walls in synovial tissue from patients with chronic inflammatory joint disease. E-selectin and TCC may also be present, but the lack of association between these two proteins suggests that the mechanism leading to a complement mediated vasculitic process is different from that causing expression of E-selectin.

Animals↗