Heavy and light chain primary structures control IgG3 nephritogenicity in an experimental model for cryocrystalglobulinemia

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3467-3472
Author(s):  
Jens-Uwe Rengers ◽  
Guy Touchard ◽  
Catherine Decourt ◽  
Sophie Deret ◽  
Hartmut Michel ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Rare Complication ◽  
Neutrophil Infiltration ◽  
In Vivo Model ◽  
Crystal Formation ◽  
Glomerular Lesions ◽  
Bona Fide ◽  
Primary Structures ◽  
Subendothelial Deposits

Crystal formation by monoclonal immunoglobulins is a well-known but rare complication of B-cell neoplasia. We have designed an in vivo model of cryocrystalglobulinemia by grafting to mice hybridoma clones producing a pathogenic monoclonal immunogloblulin (Ig) G3κ. One clone, 8A4, secreted a singular IgG3 that formed crystals both in the proliferating plasma cells and as mesangial and subendothelial deposits in the kidney glomeruli. Morphologic analysis of kidneys revealed neutrophil infiltration and endocapillary hyperplasia, while the morphology of deposits was reminiscent of those in cryocrystalglobulinemia patients. A variant clone that only differed from 8A4 by a 3–amino acid deletion in the Vκ CDR1 increased its secretion level by 7-fold and produced an abundant bona fide serum monoclonal cryoglobulin in mice, without crystal formation within tumoral cells; it yielded no subendothelial deposits but only amorphous precipitates in capillary lumens of kidney glomeruli, reminiscent of those seen in the human hyperviscosity syndrome, without other glomerular lesions. A limited variation in the Vκdomain thus proved able to increase secretion, to abrogate crystallization, and to modify patterns of glomerular lesions and deposits. Both the crystallizing and noncrystallizing IgG3κ sequences were related to previously reported murine cryoglobulins, all including a γ3 chain and canonical VH sequences. Two additional variants of 8A4 with identical VH and VL domains but having switched to IgG1 also lost crystal formation, further showing this feature of 8A4 to result from a unique 3-dimensional conformation of the complete immunoglobulin, relying on V and C domain primary structures of both chains.

Heavy and light chain primary structures control IgG3 nephritogenicity in an experimental model for cryocrystalglobulinemia

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3467-3472 ◽  
Author(s):  
Jens-Uwe Rengers ◽  
Guy Touchard ◽  
Catherine Decourt ◽  
Sophie Deret ◽  
Hartmut Michel ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Rare Complication ◽  
Neutrophil Infiltration ◽  
In Vivo Model ◽  
Crystal Formation ◽  
Glomerular Lesions ◽  
Bona Fide ◽  
Primary Structures ◽  
Subendothelial Deposits

Abstract Crystal formation by monoclonal immunoglobulins is a well-known but rare complication of B-cell neoplasia. We have designed an in vivo model of cryocrystalglobulinemia by grafting to mice hybridoma clones producing a pathogenic monoclonal immunogloblulin (Ig) G3κ. One clone, 8A4, secreted a singular IgG3 that formed crystals both in the proliferating plasma cells and as mesangial and subendothelial deposits in the kidney glomeruli. Morphologic analysis of kidneys revealed neutrophil infiltration and endocapillary hyperplasia, while the morphology of deposits was reminiscent of those in cryocrystalglobulinemia patients. A variant clone that only differed from 8A4 by a 3–amino acid deletion in the Vκ CDR1 increased its secretion level by 7-fold and produced an abundant bona fide serum monoclonal cryoglobulin in mice, without crystal formation within tumoral cells; it yielded no subendothelial deposits but only amorphous precipitates in capillary lumens of kidney glomeruli, reminiscent of those seen in the human hyperviscosity syndrome, without other glomerular lesions. A limited variation in the Vκdomain thus proved able to increase secretion, to abrogate crystallization, and to modify patterns of glomerular lesions and deposits. Both the crystallizing and noncrystallizing IgG3κ sequences were related to previously reported murine cryoglobulins, all including a γ3 chain and canonical VH sequences. Two additional variants of 8A4 with identical VH and VL domains but having switched to IgG1 also lost crystal formation, further showing this feature of 8A4 to result from a unique 3-dimensional conformation of the complete immunoglobulin, relying on V and C domain primary structures of both chains.

scholarly journals Properties of a New Food Supplement Containing Actinia equina Extract

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 945
Author(s):  
Marika Lanza ◽  
Giovanna Casili ◽  
Giovanna Loredana La Torre ◽  
Daniele Giuffrida ◽  
Archimede Rotondo ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Neutrophil Infiltration ◽  
Food Supplement ◽  
Biologically Active ◽  
In Vivo Model ◽  
Related Factor ◽  
Nuclear Factor ◽  
Anti Inflammatory

Marine species represent a great source of biologically active substances; Actinia equina (AE), an Anthozoa Cnidaria belonging to the Actinidiae family, have been proposed as original food and have already been included in several cooking recipes in local Mediterranean shores, and endowed with excellent nutraceutical potential. The aim of this study was to investigate some unexplored features of AE, through analytical screening and an in-vitro and in-vivo model. An in-vitro study, made on RAW 264.7 stimulated with H2O2, showed that the pre-treatment with AE exerted an antioxidant action, reducing lipid peroxidation and up-regulating antioxidant enzymes. On the other hand, the in-vivo study over murine model demonstrated that the administration of AE extracts is able to reduce the carrageenan (CAR)-induced paw edema. Furthermore, the histological damage due to the neutrophil infiltration is prevented, and this highlights precious anti-inflammatory features of the interesting food-stuff. Moreover, it was assessed that AE extract modulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and The nuclear factor erythroid 2–related factor 2 (Nrf-2) pathways. In conclusion, our data demonstrated that thanks to the antioxidant and anti-inflammatory properties, AE extract could be used as a new food supplement for inflammatory pathology prevention.

scholarly journals Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice

2014 ◽  
Vol 111 (02) ◽  
pp. 308-322 ◽  
Author(s):  
Rafaela da Silva ◽  
Rodrigo Fraga-Silva ◽  
Sabine Steffens ◽  
Mathias Fabre ◽  
Inga Bauer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neutrophil Infiltration ◽  
Nuclear Factor Κb ◽  
In Vivo Model ◽  
Atherosclerotic Plaques ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Beneficial Effects ◽  
Nuclear Levels

SummaryPharmacological treatments targeting CXC chemokines and the associated neutrophil activation and recruitment into atherosclerotic plaques hold promise for treating cardiovascular disorders. Therefore, we investigated whether FK866, a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with anti-inflammatory properties that we recently found to reduce neutrophil recruitment into the ischaemic myocardium, would exert beneficial effects in a mouse atherosclerosis model. Atherosclerotic plaque formation was induced by carotid cast implantation in ApoE-/- mice that were fed with a Western-type diet. FK866 or vehicle were administrated intraperitoneally from week 8 until week 11 of the diet. Treatment with FK866 reduced neutrophil infiltration and MMP-9 content and increased collagen levels in atherosclerotic plaques compared to vehicle. No effect on other histological parameters, including intraplaque lipids or macrophages, was observed. These findings were associated with a reduction in both systemic and intraplaque CXCL1 levels in FK866-treated mice. In vitro, FK866 did not affect MMP-9 release by neutrophils, but it strongly reduced CXCL1 production by endothelial cells which, in the in vivo model, were identified as a main CXCL1 source at the plaque level. CXCL1 synthesis inhibition by FK866 appears to reflect interference with nuclear factor-κB signalling as shown by reduced p65 nuclear levels in endothelial cells pre-treated with FK866. In conclusion, pharmacological inhibition of NAMPT activity mitigates inflammation in atherosclerotic plaques by reducing CXCL1-mediated activities on neutrophils. These results support further assessments of NAMPT inhibitors for the potential prevention of plaque vulnerability.

scholarly journals A New Antibiotic-Loaded Sol-Gel can Prevent Bacterial Intravenous Catheter-Related Infections

Materials ◽  
2020 ◽  
Vol 13 (13) ◽  
pp. 2946
Author(s):  
John Jairo Aguilera-Correa ◽  
Rosa Vidal-Laso ◽  
Rafael Alfredo Carias-Cálix ◽  
Beatriz Toirac ◽  
Amaya García-Casas ◽  
...  
Keyword(s):  
Foreign Body ◽  
Plasma Cells ◽  
Sol Gel ◽  
Hydrolytic Degradation ◽  
In Vivo Model ◽  
Foreign Body Giant Cell ◽  
Catheter Group ◽  
Significant Difference ◽  
Biofilm Development

The aim of this study was to evaluate the effectiveness of a moxifloxacin-loaded organic–inorganic sol-gel (A50) by locally preventing the catheter-related bloodstream infection (CRBSI) provoked by Staphylococcus epidermidis (S. epidermidis) and the effect resulting from its hydrolytic degradation on coagulation by using a rabbit in-vivo model. A50 coating can completely inhibit growth and would locally prevent CRBSI provoked by S. epidermidis. None of the coagulation blood parameters showed a significant difference constant over time between the control catheter group and the A50-coated catheter group, despite the visible silica release resulting from physiological A50 sol-gel degradation detected in serum at least during the first week. At pathological level, foreign body reaction was present in both of types of catheter, and it was characterized by the presence of macrophages and foreign body giant cell. However, this reaction was different in each group: the A50-coated catheter group showed a higher inflammation with histiocytes, which were forming granuloma-like aggregates with an amorphous crystalline material inside, accompanied by other inflammatory cells such as plasma cells, lymphocytes and mast cells. In conclusion, A50 coating a venous catheter showed excellent bactericidal anti-biofilm response since it completely inhibited S. epidermidis biofilm development and, far from showing procoagulant effects, showed slightly anticoagulant effects.

scholarly journals Platelet-Activating Factor Acetylhydrolase Prevents Myocardial Ischemia-Reperfusion Injury

Circulation ◽  
1999 ◽  
Vol 100 (suppl_2) ◽  
Author(s):  
Elizabeth N. Morgan ◽  
Edward M. Boyle ◽  
Wang Yun ◽  
John C. Kovacich ◽  
Timothy G. Canty ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Platelet Activating Factor ◽  
Neutrophil Infiltration ◽  
In Vivo Model ◽  
Area At Risk ◽  
Myocardial Ischemia Reperfusion

Background —Platelet-activating factor (PAF) is one of the most potent biological mediators of tissue injury. PAF acetylhydrolase (PAF-AH) is a recently isolated naturally occurring enzyme that hydrolyzes PAF and renders it inactive. We hypothesize that inhibition of PAF with PAF-AH will reduce myocardial ischemia-reperfusion (I/R) injury in vivo. Methods and Results —The coronary ligation model was used in New Zealand white rabbits. The large branch of the marginal coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given either 2 mg/kg of vehicle or of PAF-AH. At the completion of 120 minutes of reperfusion, percentage of necrosis, degree of neutrophil infiltration, and measurements of regional contractility were assessed. Data are expressed as the mean±SEM and compared by Student’s t test or Mann-Whitney ANOVA. Both groups of animals showed an equivalent area at risk; however, 46.7±11% was necrotic in the animal treated with vehicle. In contrast, 20.9±7.0% was necrotic in the animals treated with PAF-AH ( P <0.05). Systolic shortening and wall thickness were significantly greater in those animals treated with PAF-AH at 15, 30, 60, and 120 minutes of reperfusion ( P <0.05). Quantification of neutrophil infiltration showed a 62% reduction in the PAF-AH treated animals compared with those treated with vehicle alone. Conclusions —PAF-AH is a potent cardioprotective agent in an in vivo model of I/R injury.

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