Search PubMed⌕ Search

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.

At least 811 records · Page 45Linked to original sources
PubMed2006

Microdialysis for monitoring inflammation: efficient recovery of cytokines and anaphylotoxins provided optimal catheter pore size and fluid velocity conditions.

Microdialysis emerges as a useful tool to evaluate tissue inflammation in a number of clinical conditions, like sepsis and transplant rejection, but systematic methodological studies are missing. This study was undertaken to determine the recovery of relevant inflammatory mediators using the microdialysis system, comparing microdialysis membranes with two different molecular weight cut-offs at different flow rates. Twenty and 100 kDa pore sizes CMA microdialysis catheters were investigated using velocities of 0.3, 1.0 and 5.0 microl/min. Reference preparations for cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10; m.w. 17-28 kDa] and chemokines (IL-8, MCP-1, IP-10 and MIG; m.w. 7-11 kDa) were prepared from plasma after incubating human whole blood with lipopolysaccharide. Reference preparation for complement anaphylatoxins (C3a, C4a, C5a; m.w. 9-11 kDa) was prepared by incubating human plasma with heat-aggregated immunoglobulin G. The reference preparations were quantified for the respective inflammatory molecules and used as medium for the microdialysis procedure. Through the 20 kDa filter only the four chemokines passed, but with low recovery (3-7%) and limited to the 1.0 microl/min velocity. The recovery with the 100 kDa filter was as follows: IL-1beta = 75%, MCP-1 = 55%, MIG = 50%, IL-8 = 38%, C4a = 28%, IP-10 = 22%, C5a = 20%, C3a = 16%, IL-6 = 11, IL-10 = 8% and TNF-alpha = 4%. The highest recovery for all chemokines and anaphylatoxins were consistently at velocity 1.0 microl/min, whereas IL-1beta and IL-10 recovered most efficiently at 0.3 microl/min. Thus, microdialysis using catheters with a cut-off of 100 kDa is a reliable method to detect inflammation as judged by a defined panel of inflammatory markers. These findings may have important implications for future clinical studies.

Anaphylatoxins↗
PubMed1987

Studies on the procurement of blood coagulation factor VIII in vitro studies on blood components prepared in half-strength citrate anticoagulant.

The effect of replacing a standard citrate anticoagulant with one containing half the amount of citrate on the in vitro properties of components prepared from blood donations was investigated. This resulted in a significant improvement in factor VIII stability such that there was little loss during overnight storage, and this was reflected in the factor VIII yield in cryoprecipitate. The quality of cellular components in red cell units stored up to 35 days or platelet concentrates stored up to 7 days was not adversely affected. Although initial levels were similar to those in standard anticoagulant, the extent of fibrinopeptide A generation and complement C3 breakdown in red cell units stored for 35 days in half-strength citrate was somewhat increased.

Anticoagulants↗
PubMed1990

Possibility to improve preservation of whole blood by leukocyte-depletion before storage.

In order to evaluate the influence of leukocytes in whole blood on the standard blood bank conditions for storage, we compared several parameters of red cells, leukocytes and platelets in leukocyte-rich and leukocyte-poor whole blood over a storage period of 5 weeks. The leukocyte-depleted units were prepared by filtration with a leukocyte trapping filter (Sepacell R500A). Our data indicate improved storage conditions, made evident by significantly lower cell damage: smaller increases of elastase, beta-thromboglobulin and lactate dehydrogenase in leukocyte-depleted blood. This improvement was achieved in a simple two-bag system using only filtration, without addition of rejuvenating solutions. In addition, this procedure allows greater flexibility in the use of filtrated blood for transfusions.

Adenosine Triphosphate↗
PubMed1998

Drugs interacting with G protein alpha subunits: selectivity and perspectives.

Extracellular signal molecules as diverse as hormones, neurotransmitters and photons use a signal transduction pathway involving a receptor, a G protein and effectors. Compounds that interact directly with G proteins can mimic the receptor-G protein interaction or can block the activation of G proteins by receptors. Several binding sites exist on the G alpha protein that may be exploited for the design of synthetic stimulatory or inhibitory ligands. The effector binding site is regulated by endogenous proteins and appears to be a target for selective exogenous ligands. The GTP binding site presents a large homology within the G protein families and therefore the nucleotide analogs might not be considered as a tool to discriminate between the G protein subclasses. In contrast, different experimental strategies have substantiated the specificity in the interaction between a receptor and a G protein, the receptor binding site of G proteins should be considered as potential drug targets. Drugs interfering with this site such as mastoparan and related peptides, GPAnt-2 and suramin, are lead compounds in the design of selective G protein antagonists. Benzalkonium chloride and methoctramine have agonist or antagonist properties, depending on G protein subtypes. Such compounds would be very useful to delineate the functions of G proteins and G protein-coupled receptors, to understand some side effects of drugs used in therapy and to develop new therapeutic agents.

Amino Acid Sequence↗
PubMed1990

Biocompatibility of hemoglobin solutions. II. The inflammatory reaction of human monocytes and mouse peritoneal macrophages.

This study explored the inflammatory mechanism of toxicity of hemoglobin solutions (Hb-S). Human monocytes and mouse activated peritoneal macrophages were incubated with seven different solutions. The first four consisted of non-cross-linked bovine Hb. Of these, Hb-SI was incompletely purified of stromal phospholipids, Hb-SII was contaminated with environmental bacterial endotoxins, Hb-SIII was pure hemoglobin, and Hb-SIV was pure Hb with the addition of superoxide dismutase (SOD), catalase (CAT), and mannitol (M). The other three solutions were made of pure bovine Hb cross-linked with different agents: Hb-SV, reacted with glutaraldehyde; Hb-SVI reacted with bis-3,5-dibromosalicyl fumarate (DBSF); and Hb-SVII reacted with a ring-opened dialdehyde derivative of 5'(pyro)-phosphate of adenosine (ATP) (o-ATP). The reaction of monocytes and macrophages was studied in terms of (a) O2-derived radicals, as determined by the measurement of H2O2 and lipid peroxides; (b) complement factor C3a desArg; (c) 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin); and (d) TxB2 (stable metabolite of thromboxane) released into the culture supernatants. The most significant reactions were obtained with the solutions contaminated with stromal phospholipids or bacterial endotoxins. Pure Hb was less reactive. Further reduction in proinflammatory activity was achieved by the addition of oxygen radical-scavengers (SOD, CAT, and M), or by the cross-linking of Hb with DBSF or o-ATP.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Complement activation by alginate-polylysine microcapsules used for islet transplantation.

A foreign body reaction is frequently observed around implanted microcapsules of alginate-polylysine. Since complement activation can play a role in this reaction, we checked in vitro the ability of empty alginate-polylysine microcapsules to activate complement. Human serum was incubated with microcapsules, and complement activation was evaluated by two methods: the complement hemolytic activity (CH50) and the assay of the C3adesArg fragment. The occurrence of complement activation in the presence of microcapsules was suggested both by a CH50 decrease and by high C3adesArg levels despite C3adesArg adsorption to the capsule membrane. Capsule membrane protection against the cytotoxic effects of complement was also tested. No hemolysis occurred when microencapsulated sensitized sheep erythrocytes were incubated with activated complement. In conclusion, the microcapsule membrane can protect cells against activated complement fragments. Nevertheless, alginate-polylysine microcapsules do activate complement, and this effect must be considered for its use as an implant.

Alginates↗
PubMed1997

Generation of nitrate during dialysis as a measure of nitric oxide synthesis.

Nitric oxide (NO) is a recently identified messenger, which influences the local regulation of blood flow and platelets as well as neuronal and inflammatory pathways. Disturbed NO information might be involved in the uremic syndrome and might also cause hypotension during dialysis. To clarify these issues, we analyzed plasma and dialysis fluid concentrations of nitrate, the stable NO metabolite, in 9 patients during hemodialysis. Plasma nitrate was raised at the onset of dialysis as compared with healthy subjects (83 +/- 9 versus 26 +/- 2 mumol/L). The plasma concentration decreased to 20 +/- 2 mumol/L (p < 0.01) during the dialysis. The relative decrease was more pronounced than the relative reduction in creatinine, phosphate, and urea concentrations. A parallel decrease in nitrate was seen in effluent dialysis fluid (32 +/- 4 to 14 +/- 1 mumol/L; p < 0.01). Calculations of the amount of nitrate coming to and from the dialyzer were performed in 7 of the 9 patients, and in 5 of the 7 patients, generation of nitrate within the dialyzer could be postulated. This might explain the paradoxical venodilation noted during hemodialysis.

Aged↗
PubMed2006

Antithrombin reduces monocyte and neutrophil CD11b up regulation in addition to blocking platelet activation during extracorporeal circulation.

BACKGROUND: Patients undergoing cardiac surgery requiring cardiopulmonary bypass develop a systemic inflammatory reaction. Antithrombin III (AT) has anticoagulant effects but also shows evidence of anti-inflammatory activity. The aim of this study was to examine whether exogenous AT could reduce white blood cell activation (CD11b up regulation or elastase release), in addition to inhibiting platelet (PLT) activation and fibrin generation, during simulated cardiopulmonary bypass (sCPB), undertaken in the absence of endothelium. STUDY DESIGN AND METHODS: sCPB was carried out with minimally heparinized (2 U/mL) human blood for 90 minutes in controls and with supplementation by low-dose (1 U/mL) and high-dose (5 U/mL) AT. RESULTS: High-dose AT blunted thrombin generation during sCPB (prothrombin fragment 1.2); both doses significantly inhibited thrombin activity (fibrinopeptide A). Complement activation (C3a and C5b-9) was unaffected by AT. High-dose AT inhibited PLT activation (P-selectin expression and P-selectin-dependent monocyte-PLT conjugate formation). AT supplementation at the higher dose significantly abrogated monocyte and neutrophil CD11b up regulation and neutrophil elastase release. CONCLUSION: In addition to anticoagulant and anti-PLT effects, pharmacologic AT doses significantly blunted monocyte and neutrophil CD11b up regulation and neutrophil elastase release during sCPB, independent of endothelial effects. These data provide evidence for the direct anti-inflammatory activity of AT that has clinical relevance for CPB complications.

Antithrombin III↗
PubMed2005

Increased acylation stimulating protein concentrations in nonalcoholic fatty liver disease are associated with insulin resistance.

OBJECTIVES: As acylation stimulating protein (ASP) acts on adipocytes mainly as a paracrine factor to increase triglyceride synthesis and storage; hypothetically, it may play a similar role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). METHODS: Forty-six male patients with NAFLD (group A), age-matched 30 male patients with chronic viral hepatitis (group B) and 30 age-matched and body mass index (BMI)-matched healthy male subjects were enrolled in the study. RESULTS: Among the NAFLD patients, 10 patients (24.4%) had simple steatosis and 36 patients (69.6%) had nonalcoholic steatohepatitis (NASH). The mean levels of ASP, complement 3, insulin, C-peptide, HOMA-IR, triglyceride, and very low-density lipoprotein (VLDL) were significantly higher in group A patients than both controls and group B. ASP levels correlated significantly in a positive manner with BMI, insulin, and HOMA-IR. CONCLUSIONS: Dysregulation of the ASP pathway may have important metabolic consequences in NASH and is associated with insulin resistance.

Adipocytes↗
PubMed2005

Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic Fatty liver disease.

OBJECTIVES: The aim of the present study was to examine the systemic parameters of oxidative stress and antioxidants in patients with nonalcoholic fatty liver disease and investigate the relationship between these parameters and clinical and biochemical outcomes. METHODS: Fifty-one male patients with nonalcoholic fatty liver disease (group I), 30 age-matched and body mass index (BMI)-matched healthy male subjects, and 30 age-matched male patients with chronic viral hepatitis (group II) were enrolled in the study. RESULTS: Increased systemic levels of malondialdehyde and depletion of antioxidants such as coenzyme Q10, CuZn-superoxide dismutase, and catalase activity were observed in group I. Coenzyme Q10 and CuZn-superoxide dismutase correlated negatively with increasing necroinflammatory activity and fibrosis. Body fat was negatively associated with plasma coenzyme Q10 levels, while an inverse association was found between plasma catalase levels and TG. However, LDL was positively associated with plasma malondialdehyde levels. CuZn-superoxide dismutase levels were negatively associated with glucose, insulin, and HOMA-IR. In addition, the levels of CuZn-superoxide dismutase correlated significantly in a negative manner with BMI. CONCLUSIONS: Our results concerning correlations suggest that disturbances in BMI, body fat, and lipid metabolism may contribute to altered oxidative status in NAFLD, and insulin resistance may be related to decreased antioxidants in NAFLD as well as products of lipid peroxidation. However, although our results suggest interesting correlations, this different mostly "weak" relationships must be taken with caution.

Adult↗
PubMed1989

Interaction of campylobacter species with antibody, complement and phagocytes.

The opsonisation of four different campylobacter species for human neutrophils was studied using a chemiluminescence system and electron microscopy. Opsonisation of Campylobacter fetus, Campylobacter coli, and Campylobacter jejuni was mediated by antibody and enhanced by complement. Antibody was not, however, required for the phagocytosis of Campylobacter pylori because it activates the classical pathway of complement directly. This unusual property may be important in the pathogenesis of C pylori associated gastritis and duodenal ulcer.

Anaphylatoxins↗
PubMed2004

Differential regulation of fatty acid trapping in mouse adipose tissue and muscle by ASP.

Acylation-stimulating protein (ASP) is a lipogenic hormone secreted by white adipose tissue (WAT). Male C3 knockout (KO; C3(-/-)) ASP-deficient mice have delayed postprandial triglyceride (TG) clearance and reduced WAT mass. The objective of this study was to examine the mechanism(s) by which ASP deficiency induces differences in postprandial TG clearance and body composition in male KO mice. Except for increased (3)H-labeled nonesterified fatty acid (NEFA) trapping in brown adipose tissue (BAT) of KO mice (P = 0.02), there were no intrinsic tissue differences between wild-type (WT) and KO mice in (3)H-NEFA or [(14)C]glucose oxidation, TG synthesis or lipolysis in WAT, muscle, or liver. There were no differences in WAT or skeletal muscle hydrolysis, uptake, and storage of [(3)H]triolein substrate [in situ lipoprotein lipase (LPL) activity]. ASP, however, increased in situ LPL activity in WAT (+64.8%, P = 0.02) but decreased it in muscle (-35.0%, P = 0.0002). In addition, after prelabeling WAT with [(3)H]oleate and [(14)C]glucose, ASP increased (3)H-lipid retention, [(3)H]TG synthesis, and [(3)H]TG-to-[(14)C]TG ratio, whereas it decreased (3)H-NEFA release, indicating increased NEFA trapping in WAT. Conversely, in muscle, ASP induced effects opposite to those in WAT and increased lipolysis, indicating reduced NEFA trapping within muscle by ASP (P < 0.05 for all parameters). In conclusion, novel data in this study suggest that 1) there is little intrinsic difference between KO and WT tissue in the parameters examined and 2) ASP differentially regulates in situ LPL activity and NEFA trapping in WAT and skeletal muscle, which may promote optimal insulin sensitivity in vivo.

Adipose Tissue↗
PubMed1999

Regional specificity of ASP binding in human adipose tissue.

Obesity, in particular omental (OM) adiposity, is associated with diabetes and cardiovascular disease. Thus site-specific regulation of fat storage is important to understand. Acylation-stimulating protein (ASP) is a potent stimulator of glucose transport and triglyceride synthesis in adipocytes. In the present study, we characterized receptor binding of 125I-labeled ASP to human adipocyte plasma membranes from paired OM and subcutaneous (SC) sites in normal (N) and obese (O) male (M) and female (F) subjects (n = 24). Overall, specific binding of 125I-ASP was in the order of SC > OM and O > N (in SC tissue, particularly in F). Receptor affinity of 125I-ASP was higher [lower dissociation constant (Kd)] in SC than in OM (63.6 +/- 16.2 vs. 160.7 +/- 38.6 nM, P < 0.02), especially in F (37.0 +/- 11.1 F-N and 26.3 +/- 6.7 nM F-O) and lower (higher Kd) in male OM (291.8 +/- 116.8 M-N and 149.4 +/- 56.4 M-O). The greater binding and higher affinity of 125I-ASP binding to SC suggests that ASP may be an important factor in maintaining regional adipose tissue mass. Conversely, lower binding and receptor affinity in male OM adipose tissue may contribute to the fatty acid imbalance and metabolic complications associated with this syndrome, by reducing the efficiency of adipose fatty acid trapping by the ASP pathway.

Adipose Tissue↗
PubMed1999

Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice.

Acylation stimulating protein (ASP), a novel adipocyte-derived autocrine protein, stimulates triglyceride synthesis and glucose transport in vitro in human and murine adipocytes. In vitro, chylomicrons increase ASP and precursor complement C3 production in adipocytes. Furthermore, in vivo, ASP production from human adipose tissue correlates positively with triglyceride clearance postprandially. The aim of the present study was to determine if intraperitoneally injected ASP accelerated triglyceride clearance in vivo after a fat load in C57Bl/6 mice. ASP increased the triglyceride clearance with a reduction of the triglyceride area under the curve over 6 h (AUC(0-6)) from 102.6 +/- 30.0 to 61.0 +/- 14.5 mg. dl(-1). h(-1) (P < 0.05), especially in the latter postprandial period (AUC(3-6); 56.2 +/- 18.0 vs. 24.9 +/- 8.9 mg. dl(-1). h(-1), P < 0.025). ASP also reduced plasma glucose both in the mice with accelerated plasma triglyceride clearance and in those with relatively delayed triglyceride clearance (P < 0.025). Therefore, ASP alters postprandial triglyceride and glucose metabolism.

Animals↗
PubMed2000

Effect of regional citrate anticoagulation on leukopenia, complement activation, and expression of leukocyte surface molecules during hemodialysis with unmodified cellulose membranes.

BACKGROUND: Dialysis with complement-activating membranes is associated with leukopenia, which is related to an increased expression of adhesion molecules on leukocytes. Citrate chelates calcium and has been claimed to attenuate leukopenia. METHODS: In this study, the effects of citrate anticoagulation on leukocyte and granulocyte counts, complement activation, and the expression of CD11b, CD11c, and CD45 on the surface of granulocytes were evaluated during hemodialysis with unmodified cellulose membranes. Standard heparin was compared to citrate in three different schedules: citrate was infused to obtain a concentration of either 7 or 10 mmol/l blood. CaCl(2) was administered into the dialyzer outlet at 8. 25 mmol Ca(2+)/h (citrate 10 mmol/l) or at 11 mmol Ca(2+)/h (citrate 7 and 10 mmol/l) to reconstitute the calcium levels in the blood returning to the patient. RESULTS: The use of citrate at a high concentration (10 mmol/l) was associated with a blunted upregulation of CD11b, both at the inlet and at the outlet bloodline; for CD11c a reduced upregulation was observed on granulocytes harvested from the inlet bloodline. No effects of citrate were observed on leukopenia, granulocytopenia, or complement activation. A positive correlation between the decrease in systemic ionized Ca(2+) concentration and the increase in CD11b and CD11c expression was found. CONCLUSION: Citrate/CaCl(2) administration affects leukocyte adhesion molecule expression in a dose-dependent way; however, no significant effect could be demonstrated on leukopenia and complement activation.

Adult↗
PubMed1987

Cardiopulmonary bypass: studies on its damaging effects.

Despite the widespread safe application of cardiopulmonary bypass (CPB) for cardiac surgery, it is inherently a pathologic state. CPB produces a generalized inflammatory reaction involving at least the complement, coagulation, kallikrein, and fibrinolytic cascades. Marked alterations in organ perfusion and metabolism occur during CPB which are further affected by the perfusion flow rate. During hypothermic CPB at 20 degrees C, there is a progressive decrease in perfusion of the microcirculation at flow rates less than 1.2 liters/min/m2. Experimental studies suggest that brain oxygen consumption and resistance remain relatively constant as flow rates are reduced during hypothermia, and the brain becomes the passive recipient of proportionally more blood flow. Recent ultrafiltration studies have demonstrated a specific increase in microvascular permeability to proteins after 2 h of normothermic CPB. This provides experimental support to the well-known clinical observation of increased interstitial fluid following CPB. The development of uniformly safe CPB depends upon prevention of the abnormalities of the microcirculation and upon neutralization of the deleterious effects of inflammatory mediators.

Anaphylatoxins↗