Introduction: fat metabolism and adipose homeostasis.
Explore the source record for details and available documents.
Adipocytes↗
SEARCH · Search PubMed
Results for “Complement C3a”
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.
Acylation stimulating protein (ASP), an adipocyte autocrine: new directions.
Acylation stimulating protein (ASP) is an adipocyte-derived protein which has potent anabolic effects on human adipose tissue for both glucose and free fatty acid (FFA) storage. Our hypothesis is that: (i) ASP is produced by adipocytes in specific response to stimuli that initiate efficient fat storage; (ii) ASP interacts with a specific adipocyte receptor triggering an intracellular signalling pathway which activates triglyceride synthesis and fat storage; and (iii) that absence (ASP knockout mouse) or excess (in normal or obese mice) of ASP will result in physiological changes of plasma fat clearance and adipose tissue metabolism. The present review focuses on advances in ASP within the last 2 years with particular emphasis on these three aspects of ASP.
Adipocytes↗
Immune complexes in multiple sclerosis: relation to clinical pattern.
Using a C1q binding test, circulating immune complexes (IC) were detected in 33.3% of sera from 138 patients and in 19.4% of 124 spinal fluid samples from patients with multiple sclerosis. Most often they occur in sera alone. As a rule their detectable amount is small in sera as well as in spinal fluids. IC were observed with equal frequency during acute exacerbations and in stable phases of the disease. In patients with early MS of less than 3 months duration, IC were detected only rarely, whereas their frequency increased up to 50% in patients with longer standing disease. Immunosuppressive therapy has no influence on IC formation. Patients with immune complexes exhibited a more rapid clinical deterioration if compared as a group with IC-negativ ones. No correlations were found between immune complex formation and the CSF-IgG index or the rate of pleocytosis in spinal fluids. Neither the complement factors C3, C4, C3A nor total hemolytic complement activities (CH50) in serum were significantly decreased in patients with IC formation in serum as compared with the IC-negative group. The results demonstrate that IC formation probably is of no importance in the pathogenesis of multiple sclerosis.
Acute Disease↗
Complement-derived polypeptide C3adesArg as a mediator of inflammation at the blood-brain barrier in a new experimental cat model.
The effect of the complement-derived polypeptide C3adesArg as a mediator of inflammation in the central nervous system was examined. Twenty-five anesthetized cats received 4 mg of this polypeptide by intraventricular injection, 20 cats who served as controls received saline. Cerebrospinal fluid (CSF) was sampled 3 h after intraventricular injection and the brains were removed. For assessment of the permeability of the blood-brain barrier the CSF penetration of four antibiotics, which were given intravenously was measured. Five control animals were employed for each antibiotic (tobramycin, ampicillin, imipenem, fosfomycin), whereas six C3adesArg-treated animals were used for each antibiotic and seven for tobramycin. Besides CSF levels of glucose, the prostanoids 6-keto-prostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 were measured. The morphological examinations in the CSF sediments and histological brain sections in the C3adesArg-treated animals disclosed a distinct inflammation with leptomeningeal and perivascular infiltration of polymorphonuclear granulocytes compared to normal findings in the controls. The CSF/serum ratios of all of the antibiotics were markedly elevated compared to controls, indicating a blood-brain barrier disruption. The levels of all prostanoids were significantly higher in the treatment group than in the control group, whereas the glucose levels were lower. These findings are in accordance with a granulocytic meningitis as seen in some infections at the acute stage. It is concluded that C3adesArg acts as a mediator of inflammation in the central nervous system.
6-Ketoprostaglandin F1 alpha↗
Nifedipine inhibits granulocyte activation during cardiopulmonary bypass.
Explore the source record for details and available documents.
Adult↗
C1-inhibitor substitution therapy in septic shock and in the vascular leak syndrome induced by high doses of interleukin-2.
C1-inhibitor (C1-INH) is the major plasma inhibitor of the complement and contact systems. Activation of either system has been shown to occur in patients with septic shock and is associated with a poor outcome. Functional levels of C1-INH tend to be normal in septic patients although paradoxically this inhibitor is an acute phase protein. Moreover, levels of proteolytically inactivated C1-INH are increased in sepsis pointing to an increased turn-over. These observations suggest a relative deficiency of biologically active C1-INH in sepsis. Complement and contact activation have also been shown to occur in the vascular leak syndrome (VLS) induced by immunotherapy with the cytokine interleukin-2 (IL-2), which syndrome may be regarded as a human model for septic shock. The similarity between VLS and sepsis encompasses more than complement and contact activation since a number of other inflammatory mediators considered to play a role in the pathogenesis of septic shock, are also involved in the development of VLS. The role and the mechanisms of complement and contact activation in sepsis and in the VLS are reviewed in this paper. Initial results of intervention therapy with high doses of C1-INH in these syndromes are also reported. It is concluded that high doses of C1-INH can be safely administered to patients with septic shock or with the VLS and may attenuate complement and contact activation in these conditions. Double-blind controlled studies are needed to definitely proved these effects and to establish whether this treatment is able to reduce mortality and morbidity of these syndromes.
Blood Coagulation↗
Bioreactor based on suspended particles of immobilized enzyme.
A bioreactor for blood detoxification was developed in which oscillation-induced secondary flows suspend particles of immobilized enzyme in a reactor operating at clinically useful flowrates. Torsional oscillation of the reactor about its axis created a pair of counterrotating toroidal vortices which were readily observed in flow-visualization studies. Oscillation frequencies were selected to provide spatially uniform particle dispersion, as assessed visually. As a model system, blood deheparinization by reactors containing heparinase immobilized to agarose particles was investigated. Identical deheparinization profiles were observed in the continuous-flow reactor and in independent batch studies, done in well mixed test tubes of blood, demonstrating that the oscillating reactor design minimizes external mass transfer limitations. Identical heparin neutralization profiles and rates were also observed in the first and the second of consecutive heparin neutralization studies (0-2 h and 2-4 h, respectively) demonstrating an effective half-life of the immobilized enzyme in the oscillating reactor of at least 4 h. No significant decrease in red or white blood cell count, platelet count, or hematocrit, and clinically acceptable levels of plasma hemoglobin and activated complement were observed with 2 h (20 passes) of in vitro recirculation of human blood through the reactor. High, stable efficacy, operational stability, and excellent biocompatibility are attributed to secondary flow induced liquid-particle mixing within the oscillating reactor.
Biocompatible Materials↗
Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue.
Acylation stimulating protein (ASP) is a 14 kDa plasma protein which causes in vitro triacylglycerol synthesis in human adipocytes and fibroblasts to increase substantially. ASP was found to stimulate human adipose tissue microsomal glycerophosphate acyltransferase and diacylglycerol acyltransferase activities by 23% and 90%, respectively. However, phosphatidate phosphohydrolase activity showed no increase in activity, nor did microsomal acyl-CoA synthetase activity. Moreover, ASP did not decrease the apparent Km of diacylglycerol acyltransferase (DGAT), but rather increased its apparent Vmax suggesting direct interaction of ASP with DGAT.
Acyltransferases↗
Influence of some immune factors on the IL-6 and soluble IL-2 receptors in haemodialysed patients.
In respect to the immune deficiency state of long-term haemodialysed patients, both cytokines and their receptor disturbances have been taken into consideration. The purpose of our study was to evaluate the effect of uraemic and haemodialysis factors on the interleukin-6 and interleukin-2 soluble receptor levels and the reactivity after influenza vaccination. We have found that IL-6 and IL-2 receptor levels were statistically significantly elevated (98.8 +/- 39 pg/ml and 1557 +/- 544 U/ml, respectively) in serum of haemodialysed patients. The fact that increased immune complexes statistically correlated with soluble IL-2 receptor levels (p < 0.01) was very interesting for us. In order to study the immunological response after vaccination, 10 patients have been investigated after influenza vaccination. Plasma samples were collected before, as well as 1 and 4 weeks after vaccine administration. Antibody titres measured by haemagglutinin inhibition showed decreased antibody levels in haemodialysed patients. We conclude that the interleukin disturbance and the elevated interleukin-2 receptor levels together with the presence of circulating immune complexes can influence in some way the immune response of haemodialysed patients.
Adult↗
The pathogenetic role of impaired fatty acid trapping by adipocytes in generating the pleiotropic features of hyperapoB.
Explore the source record for details and available documents.
Adipocytes↗
Systemic blood activation with open and closed venous reservoirs.
In 20 patients undergoing coronary artery bypass grafting, we studied prospectively systemic blood activation, blood loss, and the need for donor blood when using an extracorporeal circuit equipped at random with one of two different venous reservoirs. In 10 patients we used an open venous reservoir system (ORS) consisting of a hard shell venous reservoir with an integral cardiotomy filter, and in 10 patients we used a closed reservoir system consisting of a collapsible venous reservoir and separate cardiotomy reservoir. Concentrations of complement 3a, elastase, thromboxane B2, and fibrin degradation products showed a biphasic course, especially in ORS patients. During bypass, we observed a first peak of levels of complement 3a, thromboxane B2, fibrin degradation products, and elastase, which was higher in ORS patients than in patients with the closed system, because their blood continuously contacted the foreign materials of the filter and air in the open reservoir, which was avoided in the closed reservoir. Intensive blood-foreign material contact also caused the highest (p < 0.05) hemolysis in ORS patients. The larger amount of hemolytic products in ORS patients theoretically resulted in a temporary decrease in capacity of their Kupffer cells to clear endotoxin released after aortic declamping. This theory might explain the significantly (p < 0.01) higher second peak of activated products after declamping that was observed in ORS patients. Due to increased blood activation, the largest (p < 0.001) amount of shed blood loss, greatest (p < 0.05) need for colloid-crystalloid infusion, and largest (not significant) need for donor blood were found in ORS patients (0.8 +/- 0.4 versus 0.2 +/- 0.2 units of packed cells).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
The effect of ASP on the adipocyte of the morbidly obese.
The control of triglyceride synthesis within the adipocyte is not fully understood. Insulin is considered to be the most potent stimulant of triglyceride synthesis. In this paper, we report on the effect of a small (14000 Da), basic (pI 9.0) protein isolated from human serum. This protein has been called acylation stimulating protein (ASP). It is a potent stimulant of triglyceride synthesis in adipocytes from both normal weight and morbidly obese subjects. Its stimulatory effect on adipocytes is both rapid, occurring between 15-30 min after the start of incubation, and prolonged, lasting for up to 3 hr. Compared to insulin, it is sixfold more potent in its effect on triglyceride synthesis. As well as acting on isolated cells, ASP also has a fourfold stimulatory effect on triglyceride synthesis in human adipose microsomes at a concentration of 25 micrograms/ml. This study indicates that ASP is a potent stimulant of triglyceride synthesis and therefore may play a role in the pathogenesis of morbid obesity.
Adipose Tissue↗
Interleukin-1 and osteoarthritis.
Il-1, a multifunctional monokine, can stimulate both synoviocytes and articular chondrocytes to release neutral proteases and prostaglandin E2. It is also capable of promoting bone resorption. Therefore, this molecule (or family of molecules) is likely to play an important role in the mechanism of articular cartilage destruction that occurs in degenerative arthropathies. The synovial tissue itself can produce Il-1 (Catabolin) in some conditions, such as a slight traumatism, so that the presence of local inflammation is not necessary for "Il-1-cartilage" interaction to occur. Fundamental macromolecules of cartilage (collagens, proteoglycans) exert a stimulatory effect on Il-1 production, either as such or in the form of immune complexes. Some activated complement fractions (C3a and C5a) may also be actively involved. Studies on the mechanisms which regulate Il-1 synthesis and release, as well as investigations on the response of target cells to Il-1, are presently fascinating goals that could lead to new strategies in therapeutic research.
Animals↗
Three-year treatment of familial heterozygous hypercholesterolemia by extracorporeal low-density lipoprotein immunoadsorption with polyclonal apolipoprotein B antibodies.
Familial hypercholesterolemia is a disorder of lipid metabolism associated with a highly increased risk for cardiovascular disease. Since in such patients even combined drug therapy often fails to decrease low-density lipoprotein (LDL) cholesterol levels sufficiently, extracorporeal LDL elimination has been developed. We treated eight adult patients with LDL immunoadsorption using antibodies against apolipoprotein B without additional lipid-lowering drug therapy for 3 years; this procedure was performed at weekly intervals. By one treatment session, LDL cholesterol and lipoprotein(a) levels were decreased by 55%. Under regular treatment, mean LDL cholesterol levels of 165 mg/dL between two consecutive treatment sessions could be reached, compared with 522 +/- 24 mg/dL before any treatment. As high-density lipoprotein (HDL) cholesterol levels increased under regular treatment, the LDL/HDL cholesterol ratio decreased from 13.4 to 3.4. Positive influences on plasma and whole-blood viscosity as well as on erythrocyte aggregation also seem to be beneficial with regard to retarding atherosclerosis. Very-low-density lipoprotein (VLDL) levels were reduced by approximately 50% after treatment, accompanied by a marked increase of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activity. The effects of LDL apheresis on hemostasis, complement activation transport proteins, and hematological parameters were found to be small. In addition, no side effects amounting to any major clinical relevance occurred in any of the patients. After 3 years of LDL apheresis, a decrease in the frequency of anginal chest pain and ST segment depression on exercise testing and a marked reduction of tendon xanthoma size were observed.
Adult↗
Coordinate regulation of triacylglycerol synthesis and glucose transport by acylation-stimulating protein.
Acylation-stimulating protein (ASP) is the most potent recognized stimulant of triacylglycerol synthesis in human adipocytes. However, its mechanism(s) of action have not yet been elucidated in detail. The present study examines the effects of ASP on membrane transport of glucose and fatty acids in cultured human skin fibroblasts. The data demonstrate that ASP stimulated carrier-mediated glucose transport in a time- and concentration-dependent manner, an effect that was greater than and independent of that observed with insulin. ASP increased the Vmax for glucose transport with no change in the transport Km, suggesting that ASP might result in increased sugar transporters in the plasma membrane. This finding was supported by quantitative Western blot analyses using a monoclonal antibody (G3) that demonstrated an increase in the plasma membrane content of the glucose transporter (Glut 1) with a concomitant decrease in the glucose transporter content of an intracellular membrane fraction. By contrast, ASP had no effect on specific membrane transport of fatty acids. Maximal effects of ASP on triacylglycerol synthesis were demonstrated at saturating levels of both glucose and oleate. Comparable stimulation by ASP in the absence of glucose (with or without pyruvate) was also demonstrated, although the absolute rates of triacylglycerol synthesis were substantially lower. Finally, it was shown that ASP increased the apparent Vmax for triglyceride synthesis without changing its Km. Since ASP will act in the absence of extracellular glucose, ASP must have additional actions, independent of its effect on specific membrane transport of glucose by which it accelerates intracellular triglyceride synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Biological Transport↗
Relationship between reduction of complement activation by polysaccharide surfaces bearing diethylaminoethyl groups and their degree of substitution.
The relationships between substitution of hydroxyl (OH) by diethylaminoethyl (DEAE) groups on cellulose membranes and the resulting reduction of complement activation are not clear. As a model, Sephadex has been randomly substituted with DEAE groups. Modification of 10% of the glucose units, i.e. about 3% of the groups, had no noticeable effect on the complement activating capacity of the polymer surface, whereas 20% substitution dramatically reduced it. This result could be explained in part by the fact that Sephadex-specific antibodies are not adsorbed by this modified surface. Thus, they cannot enhance complement activation as they do on Sephadex or cellulose. Comparison of our results with those published on Hemophan led us to the conclusion that a similar effect could occur. However, the degree of substitution of the membrane surface is probably greater than that of the membrane core due to the preparation process. Comparison with Sephadex substituted with other groups, or with other polymers bearing a variable density of OH groups, led us to the conclusion that, as hypothesized by Chenoweth (Artif Organs 1984; 8: 281-287), reduction of the availability of OH groups decreases complement activation, but the relationship is probably not linear. Moreover, replacement by other groups results in additional modulations due to (i) interactions between the groups and proteins responsible for formation or decay of the amplifying C3 convertase and/or (ii) decrease in recognition of the modified surface by antibodies which enhance complement activation on polysaccharides.
Adsorption↗
Clinical performance and biocompatibility of poly(2-methoxyethylacrylate)-coated extracorporeal circuits.
BACKGROUND: Poly(2-methoxyethylacrylate) is an amphiphilic organic polymer consisting of a hydrophobic backbone with pendant hydrophilic groups that has been reported to reduce protein and platelet adsorption in in vitro and ex vivo studies. METHODS: Sixty patients undergoing three-vessel coronary artery bypass grafting were divided into two equal groups. Group 1 had operation with Capiox poly(2-methoxyethylacrylate) coated SX18R oxygenators with noncoated circuits, and group 2 had operation with all noncoated circuits. Hemodynamic variables, blood and urine test results, hematologic variables, complement fractions, C3a and C4d, and interleukin-6 levels were documented preoperatively (T1), on cardiopulmonary bypass (T2), before cessation of cardiopulmonary bypass (T3), after protamine sulfate reversal (T4), and on the first postoperative day (T5). Protein electrophoresis was performed at T1 and T5. Blood cell adhesion and aggregation on fibers were analyzed with optical microscopy, and desorbed protein was evaluated quantitatively by a spectrophotometer using samples obtained when the oxygenators were dismantled after cardiopulmonary bypass. RESULTS: Platelet counts in group 1 demonstrated significant differences at T3, T4, and T5 (p < 0.05) versus group 2 and white blood cell counts in group 1 versus group 2, at counts T4 and T5. Albumin levels were significantly better preserved in group 1 at T4, and T5 and fibrinogen levels, at T3 and T5 (p < 0.05). On electrophoresis, the postoperative albumin level was 57.9% +/- 3% in group 1 versus 50.2% +/- 3% in group 2 (p < 0.05). Postoperative hemorrhage was 452 +/- 35 mL in group 1 and 612 +/- 35 mL in group 2 (p < 0.05). Duration of intubation was significantly lower (p < 0.05) in group 1, as was need of blood transfusion (p < 0.01). More platelet adhesion and aggregation were demonstrated on noncoated oxygenator fibers. The amount of desorbed protein was 0.13 +/- 0.01 mg/dL versus 0.012 +/- 0.001 mg/dL (p < 0.001) on noncoated versus coated fibers, respectively. CONCLUSIONS: Poly(2-methoxyethylacrylate)-coated oxygenators reduce platelet adhesion, platelet aggregation and protein adsorption. This surface provides a better perioperative clinical status through platelet-, albumin-, and fibrinogen-sparing effects.
Acrylates↗
Acylation-stimulating protein (ASP) regulates glucose transport in the rat L6 muscle cell line.
Acylation-stimulating protein (ASP), a human plasma protein, is a potent stimulator of triglyceride synthesis and glucose transport in both human adipocytes and fibroblasts. The purpose of the present in vitro study was to examine the effect of ASP on glucose transport in muscle cells. ASP stimulated 2-deoxy-glucose transport (2-DG) in differentiated rat L6 myotubes in a time (30 min to 24 h) and concentration dependent manner (97% increase). The magnitude of the ASP effect on glucose transport was comparable to the time- and concentration-dependent effects seen with insulin (125% increase), but was additive to insulin, pointing to involvement of differential signalling pathways. ASP stimulation was dependent on cell differentiation in that glucose transport increased by only 12% in myoblasts, comparable to the effect of insulin in myoblasts (15% increase) demonstrating selective responsiveness of the differentiated myotubes to ASP and insulin. The mechanism for the ASP induced increase in glucose transport was also examined. ASP increased the Vmax for 2-DG transport by 183% (4.02 vs. 1.42 nmol/mg cell protein/30 s; ASP vs. Control, respectively). This could be explained by an increased translocation of glucose transporters (GLUT 1, GLUT 4 and GLUT 3) to the plasma membrane surface as demonstrated by Western analysis (+43% P < 0.05, +30% P < 0.05, and +49% P < 0.05, respectively). The effects of ASP were equal to those of insulin (+47%, +26% and +53% for GLUT 1, GLUT 4 and GLUT 3, respectively) and in all cases were paralleled by comparable glucose transport increases under the same incubation conditions. After long-term stimulation (24 h), Western analysis indicated that ASP had a permissive effect on insulin stimulated increases in total GLUT3 and GLUT4 cellular transporter content. These results suggest that muscle is also responsive to ASP and that ASP may play a role in glucose metabolism in both muscle and adipose tissue.
Animals↗