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Biomedical subjects

J Egido

Publications and source records attributed to J Egido.

At least 19 recordsLinked to original sources
PubMed1992

Aggregation of human polymorphonuclear leukocytes by endothelin: role of platelet-activating factor.

The mechanisms by which endothelin-1 (ET-1) acts on polymorphonuclear leukocytes (PMN) are insufficiently known. In this study, we assessed the hypotheses that ET-1 is a PMN-aggregating agent, and that platelet-activating factor (PAF) is the principal mediator of ET-1-induced PMN aggregation. ET-1 induced dose-related PMN aggregation, which started 1 min after ET-1 exposure. Two different specific PAF receptor antagonists blocked the effect of ET-1 on PMN aggregation. In addition, ET-1 induced a significant increase in the production of PAF by PMN after 2 to 5 min of ET-1 incubation. ET-1 induced PAF release from PMN rather than accumulation. This PAF production was dependent on intra- and extracellular Ca2+. In this regard, the PAF receptor antagonists significantly blunted the ET-1-induced peak in cytosolic free Ca2+ ([Ca2+]i). Our results, therefore, indicate that ET-1 is effective in causing aggregation of human PMN and that its action appears to be mediated by PAF production via a Ca(2+)-dependent mechanism.

Azepines↗
PubMed1992

The role of interleukin 2 (IL-2) and serum-soluble IL-2 receptor cells in idiopathic IgA nephropathy.

Interleukin 2 (IL-2) plays a central role in the immune response and may be involved in the derangement of cellular immunoregulation of idiopathic IgA nephropathy (IgAN). The aim of this study was to investigate the serum levels and production of IL-2 from peripheral blood mononuclear cells (PBMC) and the distribution of IL-2 receptor cells and serum-soluble IL-2 receptor cells (sIL-2R) in patients with IgAN. Twenty-four patients with IgA nephropathy and 11 healthy controls (age and sex matched) were studied during an infection-free period without signs of clinical activity at the moment of the study. Serum IL-2 concentrations did not differ between patients and controls. The supernatant levels of IL-2 taken from 24-hr cultures of PBMC stimulated with phytohemagglutinin or tumor necrosis factor increased significantly in the patients but not in the controls. The percentage of IL-2R positive cells (CD25+) was increased in patients compared with controls. Moreover, IgAN patients had increased activated CD4+ lymphocytes when compared with the controls. Serum levels of sIL-2R were significantly higher in patients than in controls. There were no correlations among renal function, serum IgA levels, and urinary findings with cellular subsets or with IL-2 levels. However, sIL-2R was higher in the subgroup of patients with episodic macrohematuria and was closely related with the presence of red blood cells in the urinary sediment. We conclude that PBMC of IgA nephropathy patients have an overproduction of IL-2 after mitogenic stimulation, an increased helper T cell activity, increased IL-2R+ cells, and elevated serum levels of sIL-2R. These alterations are present in periods of apparent clinical inactivity. Finally, sIL-2R is closely related with hematuria, providing a good marker for disease activity. Our results suggest a pivotal role of IL-2 in cellular immune responses with regard to T cell activation in patients with IgAN.

Adult↗
PubMed1992

Familial IgA nephropathy associated with bilateral sensorineural deafness.

Alport's syndrome is the most frequent disorder with familial nephritis and deafness, but other types of nephropathy have been occasionally associated with hereditary hearing loss. The familial occurrence of IgA nephropathy has been well documented. We report a family with hereditary, bilateral, sensorineural deafness spanning four generations. Three of five members with deafness had microscopic hematuria. Renal histology of the two deaf members undergoing biopsy showed mesangial glomerulonephritis with mesangial IgA deposits, without ultrastructural abnormalities of the glomerular basement membranes. Familial nephritis with deafness should not be equated with the diagnosis of Alport's syndrome.

Deafness↗
PubMed1992

Presence of circulating antibodies against brush border antigens (Fx1A) in a patient with membranous nephropathy and bilateral pyeloureteral stenosis. Comparison with idiopathic membranous nephropathy.

In a patient with membranous nephropathy and bilateral pyeloureteral stenosis with hydronephrosis, we examined the possibility that an increase in the intratubular pressure could facilitate the passage of the Fx1A antigens to the circulation. Elevated serum anti-Fx1A antibodies were detected in this particular patient by ELISA on three occasions during the disease follow-up, even though he was in clinical remission. These antibodies reacted in vitro with the tubular brush border of a normal human kidney. The anti-Fx1A antibodies isolated from the patient's sera by affinity chromatography competed with the rabbit anti-Fx1A antisera binding to plates coated with human Fx1A antigen. In immunoblotting studies the isolated specific IgG antibodies from that patient reacted with a 180 kDa antigen of the human Fx1A and with less intensity with 75 kDa and 50-55 kDa polypeptides. In none of 12 patients with idiopathic membranous nephropathy could the circulating anti-Fx1A antibodies be demonstrated. On the whole, this particular case suggests that on some occasions increased intratubular pressure could cause the release of Fx1A antigens, facilitating an autologous immunocomplex nephritis. These antigens, by contrast, do not seem to play any role in most cases of membranous nephropathy in man.

Aged↗
PubMed1992

Involvement of platelet-activating factor and tumour necrosis factor in the pathogenesis of joint inflammation in rabbits.

We have studied the participation of platelet-activating factor (PAF) in antigen-induced arthritis in rabbits, as well as the possible co-operation between PAF and tumour necrosis factor (TNF) in their ability to induce joint inflammation when injected into the knees of healthy rabbits. The administration of two structurally different PAF receptor antagonists, BN52021 and Alprazolam, from 4 h before the intra-articular injection of ovalbumin in preimmunized rabbits, induced an important reduction in the synovial fluid volume, in the amount of cells infiltrating the articular cavity and the synovial membrane, as well as in the prostaglandin E2 (PGE2) concentration. Furthermore, proteoglycans of the articular cartilage, which were found diminished in animals with non-treated arthritis, were well preserved in rabbits treated with PAF antagonists. All the synovial fluids from joints with arthritis had detectable amounts of PAF. The injection of either TNF or PAF into the joints of normal rabbits induced a mild inflammation. When TNF was administered 1 h before PAF, a synergistic response was noted in the synovial fluid volume, in the accumulation of leucocytes, and in the amount of PGE2. The administration of BN50726, a hetrazepine with a potent PAF-receptor antagonist effect, induced a diminution in those parameters. Our results suggest that PAF may be an early and important mediator of joint damage, and that TNF can amplify the inflammatory response induced by PAF. PAF receptor antagonists could play some role in the treatment of inflammatory joint diseases.

Animals↗
PubMed1992

IL-1-like production in adriamycin-induced nephrotic syndrome in the rat.

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. A concomitance between enhanced I-a display by resident glomerular macrophages, IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis.

Animals↗
PubMed1992

T-cell alterations in immunoglobulin A nephropathy.

In the present paper are reported alterations of the cellular immunity found in 24 patients with immunoglobulin A nephropathy (IgAN). CD4+ and CD25+ cells were increased in patients in comparison with controls. The mean of interleukin-2 (IL-2) and interleukin-4 (IL-4) levels in sera were similar in patients and controls, but the levels of IL-2 in supernatants of stimulated peripheral blood mononuclear cells from patients were higher than those of controls. There were no correlations between renal function, serum IgA levels, urinary findings, cellular subsets, and IL-2 or IL-4 sera levels. These immunological data were also unrelated to the mode of clinical presentation. The results suggest a pivotal role of IL-2 in cellular immune response with regard to T-cell activation in patients with IgAN.

Adult↗
PubMed1991

Expression and synthesis of cross-reactive idiotypic antibodies by peripheral blood lymphocytes and their suppression by anti-idiotypes in patients with IgA nephropathy.

We have recently described that patients with IgA nephropathy present high serum levels of anti-BSA idiotypic antibodies that were well correlated with the existence of hematuria. Furthermore, these Id were found in circulating and renal deposited immune complexes. In the present work, we examined the expression of surface idiotypic determinants on PBL by flow cytometry and their in vitro production, using as reagent anti-idiotypic antibodies previously well characterized. The presence of cross-reactive Id-bearing cells was observed in 5 out of 6 patients studied, with frequencies ranging from 3 to 12% of lymphocytes. After 7 days of culture, the spontaneous synthesis of idiotypic antibodies by PBL was found elevated in 6 out of 13 (46%) patients. A major Id cell expression and production was noted in patients with active disease as defined by hematuria. The preincubation of PBL with 20 and 50 micrograms of anti-idiotypic antibodies/2 x 10(6) cells for 3 days induced a significant inhibition of cross-reactive Id production in a dose-dependent fashion, with a degree of suppression between 12 and 50% in five out of six patients studied. In the above assays, as negative controls, we used the anti-Id antibodies previously adsorbed on an Id-Sepharose column. On the whole, these results suggest that patients with IgA nephropathy present dysfunctions in the Id-Anti-Id network that could play an important role in the pathogenesis of this disease.

Antibodies, Anti-Idiotypic↗
PubMed1991

Inhibition by L-arginine of the endothelin-mediated increase in cytosolic calcium in human neutrophils.

The effect of endothelin (ET) on the cytosolic-free calcium [(Ca2+]i) changes in polymorphonuclear leukocytes (PMN) from normal humans and Wistar rats was investigated. ET induced a dose-related [Ca2+]i peak. This [Ca2+]i transient was blunted by TMB-8 (10(-5)M) and by Ca(2+)-free EGTA medium, therefore suggesting a role of both intracellular Ca2+ release and Ca2+ influx in the generation of the [Ca2+]i peak. Preincubation of PMN with the nitric oxide (NO)-donor L-arginine (L-Arg) markedly blocked the ET-induced [Ca2+]i transient in an enantiomerically-specific manner. A similar blunting effect of L-Arg on the fMLP (10(-7)M)-induced [Ca2+]i transient was detected. The L-Arg antagonist, NG-monomethyl-L-arginine (L-NMMA), reverted the L-Arg blocking effect on both ET- and fMLP-induced [Ca2+]i transients. These data suggest that ET has a potential role in activating Ca2+ mobilization in PMN, an effect that can be inhibited by L-Arg.

Arginine↗
PubMed1991

IgA immune aggregates stimulate platelet-activating factor and superoxide anion production by human neutrophils. A comparison with IgG aggregates.

We have examined the possibility that human polymorphonuclear cells exposed to IgA immune complexes can mediate the production of platelet-activating factor (PAF) and oxygen radicals. We found that human IgA and IgG immune aggregates stimulated, to a similar extent, PAF and O2- production by human polymorphonuclear cells (PMN) in a concentration and time dependent manner. The PAF, that was largely associated with cells, was shown to be identical to synthetic PAF, as determined by physicochemical, chromatographic and enzymatic assay. Furthermore, de novo synthesis of PAF by PMN was shown to occur by incorporation of radioactive precursors, such as [3H]acetate. The addition of normal human serum to PMN incubated with IgG aggregates resulted in a significant amount of PAF formation which was not observed with IgA aggregates. By contrast, no change was seen in PMN O2- with either aggregates. The preincubation of PMN with cytochalasin B, an inhibitor of phagocytosis, did not affect PAF and O2- production by both aggregates. The results suggest that the interaction of PMN with the IgA complexes in blood vessel walls of different tissues can result in the release of lipid mediators, such as PAF and oxygen radicals that could contribute to the inflammatory response.

Cytochalasin B↗
PubMed1991

The role of platelet-activating factor (PAF) in experimental glomerular injury.

Platelet-activating factor (PAF) is a potent autacoid that participates in inflammation and other pathophysiological processes. In this review we deal with recent evidence suggesting that PAF is a mediator that is released early during glomerular injury. PAF can be synthesized in the glomerulus by infiltrating intrinsic glomerular cells. Normal glomeruli produce PAF upon stimulation, and glomerular PAF synthesis is increased in a variety of experimental glomerulopathies. The local infusion of PAF into the renal artery of isolated blood-free kidneys induces proteinuria. PAF attracts and activates inflammatory cells. Glomerular mesangial, endothelial and epithelial cells are also targets for PAF. Therapy with specific PAF receptor antagonists has prevented or reduced proteinuria and improved glomerular inflammation in several experimental models of proliferative glomerulonephritis and minimal change nephrosis. However, the beneficial effect of administration of PAF antagonists once proteinuria is fully developed has been minimal. PAF may also play a role in the recruitment of inflammatory interstitial cells.

Animals↗
PubMed1991

Macroscopic hematuria and proteinuria preceding renal IgA deposition in patients with IgA nephropathy.

Although the clinical onset of IgA nephropathy is frequently impossible to define, macroscopic hematuria apparently heralds the onset of the disease in some patients. We describe the clinical course and renal histologic findings of four adults with IgA nephropathy who were diagnosed by the characteristic immunohistologic features in a second renal biopsy specimen. IgA was not detected in the initial renal biopsy specimens obtained 9 months to 4 years earlier. The first renal biopsy had been performed to evaluate macroscopic hematuria (recurrent in three patients), accompanied by pathologic proteinuria in two patients. Our observations suggest that the pathognomonic immunohistologic findings of IgA nephropathy may follow the clinical onset and raise questions about the presumed pathogenetic role of IgA in the early stages of this disease.

Adult↗
PubMed1991

Involvement of lipid mediators in the pathogenesis of experimental nephrosis in rats: its pharmacological modulation.

The administration of a single-injection of Adriamycin (ADR) to rats results in marked proteinuria and glomerular morphological changes that are similar to minimal change disease in humans. We have hypothesized that Adriamycin, by itself or through the release of some mediators from resident glomerular cells, could provoke a damage to epithelial glomerular cells. Sprague-Dawley rats received a single injection of Adriamycin, 7.5 mg/kg bw, allocated randomly in several groups and treated throughout 2 weeks of follow-up. All control nontreated animals developed important nephrotic syndrome and degenerative lesions of epithelial glomerular cells. Isolated glomeruli from animals injected with adriamycin 14 days before synthesized thromboxane (TxB2) and platelet activating factor (PAF) in amounts above the rates of control glomeruli. Animals treated with three structurally different PAF receptor antagonists did not present proteinuria or only to a very low extent (p less than 0.0005). In these rats no alterations in epithelial cells were noted. Furthermore, no significant changes in the TxB2 production were noted in rats treated with BN 52021, a PAF receptor antagonist. Leukotrienes also seem to participate since treatment with a 5-lipoxygenase inhibitor partially corrected proteinuria. Moreover, glomeruli from animals with nephrosis and treated with this compound presented only a discrete reduction in the PAF synthesis. On the whole, these data suggest a key role for PAF in the pathogenesis of adriamycin nephropathy. Other lipid meditors, released in cascade simultaneously or thereafter, could perpetuate the renal damage.

Animals↗