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N Ronda

Publications and source records attributed to N Ronda.

At least 19 recordsLinked to original sources
PubMed2003

Normal human IgG prevents endothelial cell activation induced by TNFalpha and oxidized low-density lipoprotein atherogenic stimuli.

Normal human immunoglobulin G (IgG) has anti-inflammatory and immuno-regulatory properties, which are exploited in the therapy of selected diseases. A putative mechanisms of action is the direct regulation of endothelial cell function by natural antiendothelial cell antibodies. Endothelium activation is a critical event in atherosclerosis. We have verified the ability of normal human IgG to modulate endothelial responses to the atherogenic stimuli tumour necrosis factor-alpha (TNFalpha) and oxidized low-density lipoproteins (oxLDL) in vitro. Confocal microscopy was used to visualize vascular cell adhesion molecule-1 (CD106) expression on endothelial cells, cytoplasmic free calcium ([Ca++]i) modifications and fluorescein-coupled oxLDL internalization. Cytokine secretion was measured by ELISA on cell supernatants. IgG prevented TNFalpha induced CD106 membrane expression and an increase in [Ca++]i, and inhibited the secretion of interleukin-6 (IL-6) and macrophage-colony-stimulating factor (M-CSF). IgG also inhibited CD106 expression induced by oxLDL and one pathway of their internalization, but were ineffective on oxLDL induced [Ca++]i rise and apoptosis. F(ab)'2 fragments from IgG, but not monoclonal IgG, reproduce IgG effects. These findings point to a regulatory role for specific antibodies included in circulating normal IgG towards proinflammatory responses of endothelial cells in atherogenesis and suggest possible development of new therapeutic strategies.

Apoptosis↗
PubMed1999

Natural anti-endothelial cell antibodies (AECA).

Natural AECA constitute a pool of autoantibodies circulating in healthy subjects, which react with a restricted and conserved set of endothelial antigens and establish idiotypic interactions within the immunoglobulin networks. Normal IgG interacts with living endothelial cells and is internalized with a mechanism involving microtubules and resembling that of ligand-receptor internalization. IgG-endothelial cell interaction appears to be dependent on the variable region of antibodies and is followed by modifications of endothelial cell function. Natural AECA increase anti-inflammatory properties of endothelial cells through the selective inhibition of thromboxane A2, endothelin and metalloproteinase-9 secretion, and also through the inhibition of endothelial cell proinflammatory response to TNF-alpha. We have gathered evidence demonstrating that natural AECA constitute a strictly controlled autoantibody pool, interact with living endothelial cells and take part in the regulation of endothelial function, through direct anti-inflammatory effects.

Antibody Specificity↗
PubMed1997

Binding and internalization of human IgG by living cultured endothelial cells.

Interactions between circulating IgG and endothelial cells (EC) in humans have been described only in conditions associated with pathologic immunoglobulins and/or activated or damaged EC. In this study we provide evidence that normal human IgG includes one/some antibody species that bind to and are internalized by living EC in culture. This novel function of EC and natural autoantibodies is of potential importance for the understanding of physiologic interactions between vessels and the immune system and for the clarification of pathogenesis of vasculitis and mechanisms of action of pooled IgG used in the therapy of such conditions.

Autoantibodies↗
PubMed1995

Normal human polyspecific immunoglobulin G (intravenous immunoglobulin) modulates endothelial cell function in vitro.

We have analysed the in-vitro effect of pooled normal polyspecific immunoglobulin G (IVIg) and F(ab')2 fragments of IVIg on the secretion of prostacyclin (PGI2), thromboxane A2 (TxA2), and endothelin from cultured human umbilical vein endothelial cells. The stable metabolites, 6-keto-PGF1 alpha and TxB2, as well as endothelin, were measured by radioimmunoassay after extraction from the culture supernatants. IVIg inhibited TxB2 and endothelin secretion in a dose-dependent manner, but not that of 6-keto-PGF1 alpha. Therefore the ratio of 6-keto-PGF1 alpha/TxB2 increased (+600%). The effect of F(ab')2 fragments prepared from IVIg was similar to that observed with IVIg, indicating that the effect of IVIg was mediated by the variable region of immunoglobulin. The results suggest that part of the effects of IVIg in inflammatory vasculitis may be due to a modification of the PGI2/TxA2 ratio and inhibition of endothelin secretion, and that natural IgG antibodies may participate in the homeostatic process of endothelium under physiological conditions.

Cells, Cultured↗
PubMed1994

Selectivity of recognition of variable (V) regions of autoantibodies by intravenous immunoglobulin (IVIg).

In the present study, we demonstrate that intravenous immunoglobulin (IVIg) is capable of binding to variable (V) regions of anti-endothelial cell antibodies (AECA) of healthy donors and patients with systemic lupus erythematosus (SLE). Among V regions of AECAs, IVIg selectively recognized certain idiotypes expressed by the autoantibodies of a given individual, in the case of both natural and SLE-associated AECAs. These observations provide new and direct evidence that IVIg interacts idiotypically with V regions of autoantibodies and that the efficacy of such interaction depends on individual autoantibody specificity. Our findings may be relevant for the understanding of the mechanisms that control expression of natural autoantibody activity in serum and for that of the differences in response to IVIg therapy that are seen between patients with autoimmune disease.

Antibody Specificity↗
PubMed1994

Analysis of natural and disease-associated autoantibody repertoires: anti-endothelial cell IgG autoantibody activity in the serum of healthy individuals and patients with systemic lupus erythematosus.

The present study demonstrates that natural IgG with anti-endothelial cell activity is present in the serum of healthy individuals and in pooled normal human Ig. By using a novel method that allows for the simultaneous and quantitative assessment of reactivities of antibodies with a large number of antigens in tissues, we observed that natural anti-endothelial cell antibody (AECA) recognizes a restricted set of self antigens in endothelial cells that is conserved among healthy individuals. The extent to which natural AECA activity is expressed in serum and the pattern of reactivity of AECA with endothelial cell antigens showed little variability between individuals. Analysis of AECA in the serum of patients with systemic lupus erythematosus (SLE) revealed a higher amount of activity and a wider spectrum of antigenic specificities than that recognized by natural antibodies in endothelial cell extracts. AECA activity of IgG in whole serum was lower than that of purified IgG in the case of healthy individuals and showed little variation among individuals. In contrast, no difference was found between AECA activity of purified IgG and that of IgG in patients' serum suggesting that SLE sera lack the factors that control expression of AECA activity in the serum of healthy individuals. Our results indicate that natural autoantibodies recognize a restricted and conserved set of self antigens. Our observations further suggest that defective regulation of the expressed autoreactive B cell repertoire is the basis for expansion of novel clonal specificities and enhanced autoantibody activity in serum of patients with autoimmune disease.

Autoantibodies↗
PubMed1994

Antineutrophil cytoplasm antibodies (ANCA) of IgA isotype in adult Henoch-Schönlein purpura.

ANCA are associated with certain forms of systemic vasculitis, and have been reported previously to be of the IgG and IgM isotype. We examined the possible association between IgA ANCA and the IgA-related diseases Henoch-Schönlein purpura (HSP) and IgA nephropathy (IgAN). IgA and IgG ANCA were detected by isotype-specific solid-phase assays with a crude neutrophil extract, and their presence was confirmed by antigen-specific fluid-phase competitive inhibition tests and by indirect immunofluorescence. The possible interference by IgA rheumatoid factor was excluded. IgA ANCA were detected in sera from 11/14 HSP patients (79%), from 1/30 IgAN patients (3%), from 1/40 patients with vasculitides classically associated with IgG ANCA (2.5%), and in none of 60 sera from healthy blood donors. IgG ANCA were present with IgA ANCA in three patients with HSP. Only one HSP serum had anti-myeloperoxidase (MPO) activity by both IgA and IgG isotype-specific ELISA, and none was positive for proteinase 3 (PR3). Western blot analysis performed with neutrophil extract showed that the four strongest IgA ANCA-positive HSP sera reacted with a 51-kD protein; Western blot performed on cellular fractions showed that this protein is primarily membrane-associated, and different from fibronectin. Our study suggests that adult HSP is closely associated with circulating IgA ANCA, which may be directed against a different autoantigen than that recognized by IgG ANCA.

Adolescent↗
PubMed1993

Association of ANCA isotype and affinity with disease expression.

The association of ANCA isotype and affinity with disease expression is reviewed and new data on IgA ANCA levels and affinity in relation to disease activity are presented. Differences in the IgG ANCA subclass distribution exist between active disease and remission, with high affinity IgG3 ANCA present at the onset of disease. IgM ANCA, with or without associated IgG ANCA, correlates with pulmonary haemorrhage and disappears at remission. IgA ANCA are mainly found in patients presenting with Henoch-Schönlein purpura (HSP), and are directed against a distinct autoantigen of approximately 50 kD. The level and affinity of IgA ANCA also correlate with disease activity in HSP. Isotype as well as antibody specificity appear to be major determinants of disease expression.

Adult↗
PubMed1993

Anti-neutrophil cytoplasm antibodies (ANCA) increase neutrophil adhesion to cultured human endothelium.

ANCA have been demonstrated to activate normal neutrophils in vitro. This study demonstrates that ANCA positive IgG and Fab2 fragments increase the adhesion of normal neutrophils to cultured human umbilical vein endothelium (HUVEC), and that preincubation of the endothelial monolayers with tumour necrosis factor (TNF) to activate the endothelium enhances this effect. Preincubation of neutrophils with anti-CD18 monoclonal antibodies inhibited adhesion, suggesting that the observed effect was integrin mediated.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Intravenous immunoglobulin therapy of autoimmune and systemic inflammatory diseases.

The proven beneficial effect of intravenous immunoglobulins (IVIg) in certain autoimmune disorders has led to the development of clinical trials in other autoimmune and systemic inflammatory diseases. In parallel, experimental studies are being carried out to better understand the mechanisms of action of IVIg. In this review, we discuss the clinical use of IVIg in autoimmune disorder and the possible mechanisms by which IVIg may be effective in the various diseases. A better understanding of the mechanisms of action of IVIg in autoimmune disease will allow optimization of their use as a therapeutic alternative to conventional immunosuppression.

Autoimmune Diseases↗
PubMed1990

Hypophosphatemia in course of chronic obstructive pulmonary disease. Prevalence, mechanisms, and relationships with skeletal muscle phosphorus content.

Serum phosphorus levels (Ps), dietary intake of phosphorus, and renal phosphate handling indexes were evaluated in 158 patients with chronic obstructive pulmonary disease (COPD) of varying degrees of severity; moreover, skeletal muscle phosphorus content (Pm) was measured in muscle samples obtained by quadriceps femoris needle biopsy in 14 of the same patients. Hypophosphatemia (Ps less than or equal to 2.5 mg/dl) was found in 34 (21.5 percent) of 158 patients without differences between groups of COPD patients presenting increasing severity of respiratory illness. No relationship was found between serum levels and dietary intake of phosphorus; hypophosphatemia was associated with low renal phosphate threshold (TmPO4/GFR) values in 31 (91 percent) of 34 patients. The prevalence of hypophosphatemia was significantly higher among COPD patients taking one or more drugs commonly used in COPD and known as negatively influencing renal phosphate handling: xanthine derivatives, corticosteroids, loop diuretics, and beta 2-adrenergic bronchodilators. Short-term administration of therapeutic doses of these drugs in COPD patients previously not taking any drug reduced TmPO4/GFR values; phosphaturic effect of short-term theophylline administration on renal phosphate handling was additive to that of long-term assumption of the drug. Muscle phosphorus content was both reduced in COPD patients as compared with control subjects and significantly correlated to serum phosphorus levels and to TmPO4/GFR values. The present investigation revealed a high prevalence of hypophosphatemia among COPD patients as well as a defect in renal phosphate reabsorption secondary, at least in part, to pharmacologic therapy. Moreover, it also suggests that in COPD patients muscle phosphorus content is likely to be reduced in presence of hypophosphatemia.

Adult↗
PubMed1990

A comparative clinical study on the effects of cardiopulmonary bypass with different flows and pressures on skeletal muscle cell metabolism in patients undergoing coronary bypass grafting.

This study compares the effects of cardiopulmonary bypass with different flows and pressures on intracellular energy metabolism, acid-base equilibrium, and muscle water compartments in two groups of patients undergoing coronary artery bypass grafting. Eighteen patients (16 men and two women aged 54 +/- 7 years, New York Heart Association class I-II) undergoing low flow (flow rate 1.5 L/min/m2 at 26 degrees C), low pressure (mean arterial pressure 40 to 60 mm Hg) cardiopulmonary bypass, as well as 10 age-matched and sex-matched patients undergoing normal flow (flow rate 2.2 L/min/m2 at 26 degrees C), normal pressure (mean arterial pressure 60 to 80 mm Hg) bypass were studied. Intracellular acid-base equilibrium (intracellular pH and intracellular bicarbonate), cell energetics (adenosine triphosphate, diphosphate, and monophosphate, phosphocreatine, and lactate), and muscle water compartments were evaluated in specimens of the quadriceps femoris muscle obtained by needle biopsy before and at the end of cardiopulmonary bypass. In both the low flow-low pressure and normal flow-normal pressure groups, adenosine triphosphate levels were unchanged at the end of bypass, whereas phosphocreatine concentration was decreased; muscle total water and extracellular water increased without variations of intracellular water; muscle and plasma lactate increased as intracellular bicarbonate decreased; intracellular pH values remained unchanged. The present study suggests the following: (1) Cardiopulmonary bypass is associated with the overall preservation of intracellular compartment metabolism in skeletal muscle (about 40% of body cell mass) of patients undergoing coronary bypass grafting, even though low phosphocreatine values and increased plasma and muscle lactate values found at the end of bypass could be an expression of cell functional reserve exhaustion; (2) the effects of cardiopulmonary bypass on cell metabolism are comparable, regardless of the flows and pressures used.

Blood Pressure↗