Quantitation of components of the alternative pathway of complement (APC) by enzyme-linked immunosorbent assays

Oppermann, Martin; Baumgarten, H.; Brandt, E. Michael; Gottsleben, Walter; Kurts, Christian; Götze, Otto

doi:10.1016/0022-1759(90)90358-3

Cited by 45 publications

(26 citation statements)

References 28 publications

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“…Fasting glucose 30 and triglyceride 31 levels were determined by routine biochemical methods. Insulin and leptin were determined in serum by commercially available radioimmunoassays (Sorin, Biomedica, and Wak-Chemie, Medical GmbH, respectively) and adipsin by an ELISA according to Oppermann and coworkers, 32 with the following modifications: for coating the plates, monoclonal anti-human factor D IgG (4 g/mL D10/4, Connex GmbH) in 5.5 mmol/L Na 2 CO 3 , 35 mmol/L NaHCO 3 , and 0.01% thimerosal (pH 9.6) was used. Instead of gelatin, 1% BSA was used in the blocking and sample dilution buffers.…”

Section: Anthropometric and Laboratory Measurementsmentioning

confidence: 99%

Impact of Adipose Tissue on Plasma Plasminogen Activator Inhibitor-1 in Dieting Obese Women

Mavri

Stegnar²,

Krebs³

et al. 1999

ATVB

105

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Abstract-The increased incidence of cardiovascular diseases in obese subjects could be partially attributed to impaired fibrinolysis due to elevated plasma levels of tissue plasminogen activator inhibitor 1 (PAI-1). The associations between changes in plasma PAI-1, metabolic variables, and adipose tissue during weight loss and regain were studied in 52 healthy, premenopausal, obese women participating in a weight reduction program with a hypocaloric diet. PAI-1, insulin, triglyceride, leptin, and adipsin levels were determined at entry, after the first week, after completion of the program, and after 5 months of follow-up. In the 33 obese women who completed the program, decreases in PAI-1 antigen (Ϫ54%), PAI activity (Ϫ74%), and leptin (Ϫ51%), but not of adipsin, were observed. Changes in PAI-1 were associated with changes in body mass index (BMI), body fat, leptin, and insulin. The decreased level of PAI-1 remained low after follow-up in the 14 women who maintained their reduced weight but increased in the 16 women who regained weight. This increase in PAI-1 was correlated with an increase in body fat and leptin. On multivariate analysis, BMI was the major determinant of PAI-1 level. In conclusion, during weight reduction with a hypocaloric diet, the decrease in PAI-1 is more closely related to changes in adipose tissue than to changes in metabolic variables, suggesting a significant role for adipose tissue in regulating plasma levels of PAI- A n increased level of plasma tissue plasminogen activator inhibitor 1 (PAI-1), the main regulator of blood fibrinolytic activity, 1 has repeatedly been shown to be associated with obesity. 2,3 PAI-1 is positively correlated with body mass index (BMI) in men 4 as well as in women. 5,6 PAI-1 is further correlated with other measures of obesity, such as waist-tohip circumference ratio (WHR), reflecting abdominal fat, and with several metabolic factors, such as plasma triglycerides and insulin. [7][8][9] It is, however, unclear which of the these parameters is the major determinant of plasma PAI-1. Elevated PAI-1 levels were found in young survivors of myocardial infarction and were also predictive for future cardiovascular events. 10,11 In obese women, mortality due to cardiovascular events is increased 4-fold compared with lean women. 12 Therefore, the abnormal expression of PAI-1 in obesity might represent 1 of the mechanisms through which the risk for the development of cardiovascular diseases is increased in obese individuals.There is ample evidence that weight loss due to a lowcalorie diet or fasting affects fibrinolysis by reducing plasma PAI-1 levels. [13][14][15][16][17][18][19] The decrease in PAI-1 could be attributed to either a reduction in body weight and body fat or alterations in blood lipids and/or insulin levels. The former presumption is supported by data showing high concentrations of PAI-1 mRNA in mouse fat tissue 20 and by the demonstration of PAI-1 mRNA in mouse adipocytes. 21 PAI-1 is also synthesized by cultured 3T3-L1 cells, an adipocyte line. 21 Th...

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Section: Anthropometric and Laboratory Measurementsmentioning

confidence: 99%

Impact of Adipose Tissue on Plasma Plasminogen Activator Inhibitor-1 in Dieting Obese Women

Mavri

Stegnar²,

Krebs³

et al. 1999

ATVB

105

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“…Concentrations of immunoglobulin κ light chain were measured by immunoassay (Freelite, The Binding Site, Birmingham, UK). Complement factor D concentrations were measured by ELISA [17]. Dialysate albumin concentrations were measured by enzyme immunoassay (Alpco, Windham, NH, USA).…”

Section: Methodsmentioning

confidence: 99%

Differences in solute removal by two high-flux membranes of nominally similar synthetic polymers

Ouseph

Hutchison

Ward

2008

Nephrology Dialysis Transplantation

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Background. Membranes fabricated from nominally similar polymers may be markedly different in chemical composition, morphology and geometry. To examine the relative importance of these factors to dialyzer performance, the removal of small and large uraemic toxins was determined for dialyzers containing 'polysulfone' membranes of different composition and morphology, with and without fibre undulations. Methods. Total removal and instantaneous clearances of urea, phosphorus, β 2 -microglobulin, leptin, angiogenin, complement factor D and immunoglobulin κ light chain were determined in randomized cross-over studies. Total solute removal was assessed from the pre-to post-dialysis change in plasma concentration and the total amount of solute recovered in the dialysate. Trapping of solute at the membrane was determined as the difference between solute lost from plasma water and solute recovered in the dialysate. Results. Total removal of urea and phosphorus was independent of the membrane composition and structure. Large molecule removal differed significantly between the two membranes, particularly for β 2 -microglobulin. The importance of trapping at the membrane as a mechanism of β 2 -microglobulin removal also differed significantly between the two membranes, with trapping being less important for the membrane with the greatest β 2 -microglobulin removal. As molecular size increased, the contribution of trapping at the membrane to solute removal increased and the difference between the two membranes decreased. Conclusions. High-flux membranes fabricated from nominally similar polymers may differ significantly in their ability to remove low molecular weight protein uraemic toxins.

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“…The normal concentration range of factor Bb is 0.4 to 1.0 g/mL, 31 the mean 0.65 Ϯ 0.23 g/mL, 33 and high levels were found in septic shock (3.7 Ϯ 2.1 g/mL 34 ). Pretreatment levels of factor Bb were within the normal range in 2 amyopathic patients ( Figure 6A-B) and twice as high in one of the myopathic patients studied ( Figure 6C).…”

Section: Attenuation Of Complement Amplification By Lowering the Concmentioning

confidence: 99%

Intravenously applied IgG stimulates complement attenuation in a complement-dependent autoimmune disease at the amplifying C3 convertase level

Lutz

Stammler

Bianchi

et al. 2004

Blood

104

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Intravenously applied normal human immunoglobulin G (IgG) has anti-inflammatory effects in the treatment of autoimmune diseases. Systemic inflammation can originate from an overreacting amplification loop of the complement system. In blood, C3b 2 -containing complexes maintain complement amplification much better than the extremely short-lived C3b. Therefore, in patients with the complement-dependent autoimmune disease, dermatomyositis, we studied whether intravenously applied normal human IgG (IVIG) stimulated in vivo inactivation of these complexes. In the course of IVIG treatment, clinically effective in 6 of 8 patients, the concentration of C3b 2 -containing complexes dropped to 37% ؎ 14% (n ‫؍‬ 6) of the pretreatment level when having infused 0.5 g IgG/kg body weight, increased marginally and in parallel to factor Bb thereafter until full-dose IgG was infused. By day 14 following infusion of 2 g IgG/kg body weight the concentration of C3b 2 -containing complexes was 66% ؎ 19%. The plasma concentration of C3 remained constant in myopathic or increased by 15% to 20% in amyopathic patients. In contrast to this, IVIG infusion was associated with consumption of up to 40% of plasma C4 at day 1 to 2 after completion of IVIG infusion. Thus, IVIG had an immediate and long-lasting attenuating effect on complement amplification in vivo, despite the fact that it induced classical complement pathway activation. IntroductionIntravenously applied human immunoglobulin G (IgG) has an immunomodulatory potential. 1 This effect might in part be due to modulation of phagocytic cells either by altering autocrine or paracrine cytokines through the action of anticytokine antibodies 2,3 or alterations of cell receptor functions 4 or expression. 5,6 Intravenously applied human IgG (IVIG) is, however, similarly beneficial in autoimmune diseases that are associated with excessive complement activation via the classical pathway and the amplification loop. [7][8][9] Such complement activation is proinflammatory by generating C3b in excess. C3b, the active form of C3, binds covalently to targets and promotes generation of C3 convertases, which, in turn, consume C3 and allow assembly of C5 convertase. Elevated C3/C5 convertase activity 10 produces locally proinflammatory anaphylatoxins, C3a/C5a, and generates C5b that can initiate formation of the membrane attack complex on target cells. Finally, insertion of C5b to 7 and C9 into membranes of nucleated cells can result in activation of the arachidonic acid pathway that forms mediators of inflammation. 11 IVIG at high doses is able to displace nascent C3b from tissue-bound immune complexes to the fluid phase 12,13 by serving as a preferential binding site for C3b. 14 Although this process reduces local complement activation, it does not stop systemic complement amplification. Indeed, nascent C3b deposited to fluid-phase IgG primarily forms C3b 2 -IgG complexes. 14 These complexes represent potent activators of the amplification loop and are, on a molar basis, more efficient activators tha...

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Quantitation of components of the alternative pathway of complement (APC) by enzyme-linked immunosorbent assays

Cited by 45 publications

References 28 publications

Impact of Adipose Tissue on Plasma Plasminogen Activator Inhibitor-1 in Dieting Obese Women

Impact of Adipose Tissue on Plasma Plasminogen Activator Inhibitor-1 in Dieting Obese Women

Differences in solute removal by two high-flux membranes of nominally similar synthetic polymers

Intravenously applied IgG stimulates complement attenuation in a complement-dependent autoimmune disease at the amplifying C3 convertase level

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