RESUMEN

Typical haemolytic uraemic syndrome (HUS) is caused by Shiga toxin (Stx)-producing Escherichia coli infections and is characterized by thrombotic microangiopathy that leads to haemolytic anaemia, thrombocytopenia and acute renal failure. Renal or neurological sequelae are consequences of irreversible tissue damage during the acute phase. Stx toxicity and the acute inflammatory response raised by the host determine the development of HUS. At present there is no specific therapy to control Stx damage. The pathogenic role of reactive oxygen species (ROS) on endothelial injury has been largely documented. In this study, we investigated the in-vivo effects of Stx on the oxidative balance and its contribution to the development of HUS in mice. In addition, we analysed the effect of anti-oxidant agents as therapeutic tools to counteract Stx toxicity. We demonstrated that Stx induced an oxidative imbalance, evidenced by renal glutathione depletion and increased lipid membrane peroxidation. The increased ROS production by neutrophils may be one of the major sources of oxidative stress during Stx intoxication. All these parameters were ameliorated by anti-oxidants reducing platelet activation, renal damage and increasing survival. To conclude, Stx generates a pro-oxidative state that contributes to kidney failure, and exogenous anti-oxidants could be beneficial to counteract this pathogenic pathway.

Asunto(s)

RESUMEN

Tolerance to lipopolysaccharide (LPS) constitutes a stress adaptation, in which a primary contact with LPS results in a minimal response when a second exposure with the same stimulus occurs. However, active important defence mechanisms are mounted during the tolerant state. Our aim was to assess the contribution of polymorphonuclear neutrophils (PMN) in the clearance of bacterial infection in a mouse model of tolerance to LPS. After tolerance was developed, we investigated in vivo different mechanisms of bacterial clearance. The elimination of a locally induced polymicrobial challenge was more efficient in tolerant mice both in the presence or absence of local macrophages. This was related to a higher number of PMN migrating to the infectious site as a result of an increased number of PMN from the marginal pool with higher chemotactic capacity, not because of differences in their phagocytic activity or reactive species production. In vivo, neutrophils extracellular trap (NET) destruction by nuclease treatment abolished the observed increased clearance in tolerant but not in control mice. In line with this finding, in vitro NETs formation was higher in PMN from tolerant animals. These results indicate that the higher chemotactic response from an increased PMN marginal pool and the NETs enhanced forming capacity are the main mechanisms mediating bacterial clearance in tolerant mice. To sum up, far from being a lack of response, tolerance to LPS causes PMN priming effects which favour distant and local anti-infectious responses.

Asunto(s)

RESUMEN

Las neumonías intersticiales idiopáticas, cuyos hallazgos histológicos y radiológicos revisamos, se incluyen entre las enfermedades difusas del parénquima pulmonar y, aunque pueden afectar a otros compartimentos, el intersticio pulmonar es el sustrato inicial de la lesión del parénquima por diversos patrones de inflamación y fibrosis. La clasificación actual, propuesta en 2002 como un documento de consenso internacional multidisciplinario auspiciado por la American Thoracic Society y la European Respiratory Society incluye 7 entidades. Basada en criterios histológicos, cada patrón histológico se asocia con un patrón de imagen. Son un grupo de entidades de etiología desconocida con características comunes y rasgos diferenciales que permiten individualizarlas como enfermedades con pronóstico y tratamiento diferentes. Como formas idiopáticas son infrecuentes, pero comparten sustrato morfológico con otras enfermedades de causa conocida más frecuentes, que es necesario excluir para alcanzar el diagnóstico definitivo. Por ello, es importante que el radiólogo esté familiarizado con sus hallazgos de imagen característicos (AU)

A review is presented on the histological and radiological findings in idiopathic interstitial pneumonias, which are included among the diffuse parenchymal lung diseases. Although they may affect other compartments, the lung interstitium is the initial substrate of the parenchymal lesion due to different patterns of inflammation and fibrosis. The current classification, proposed in 2002 as an international multidisciplinary consensus document promoted by the American Thoracic Society and the European Respiratory Society, includes 7 conditions. Based on histological criteria, each histological pattern is associated with an image pattern. They are a group of conditions of unknown origin with common characteristics and differential features that enable them to be individualised as diseases with a different prognosis and treatment. They are rare as idiopathic forms, but share a morphological substrate with other more common diseases of unknown cause, which means they have to be excluded to reach a definitive diagnosis. For this reason it is important that the radiologist is familiar with their characteristic imaging finding (AU)

Asunto(s)

RESUMEN

A review is presented on the histological and radiological findings in idiopathic interstitial pneumonias, which are included among the diffuse parenchymal lung diseases. Although they may affect other compartments, the lung interstitium is the initial substrate of the parenchymal lesion due to different patterns of inflammation and fibrosis. The current classification, proposed in 2002 as an international multidisciplinary consensus document promoted by the American Thoracic Society and the European Respiratory Society, includes 7 conditions. Based on histological criteria, each histological pattern is associated with an image pattern. They are a group of conditions of unknown origin with common characteristics and differential features that enable them to be individualised as diseases with a different prognosis and treatment. They are rare as idiopathic forms, but share a morphological substrate with other more common diseases of unknown cause, which means they have to be excluded to reach a definitive diagnosis. For this reason it is important that the radiologist is familiar with their characteristic imaging findings.

Asunto(s)

RESUMEN

Sepsis and septic shock can be caused by Gram-positive and -negative bacteria and other microorganisms. In the case of Gram-negative bacteria, endotoxin, a normal constituent of the bacterial wall, also known as lipopolysaccharide (LPS), has been considered as one of the principal agents causing the undesirable effects in this critical illness. The response to LPS involves a rapid secretion of proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, interferon (IFN)-γ and the concomitant induction of anti-inflammatory mediators such as IL-10, transforming growth factor (TGF)-ß or glucocorticoids, which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the main cause of the non-specific humoral and cellular immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that mifepristone (RU486), a known glucocorticoid receptor antagonist, could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS immunosuppressed mice, suggesting the involvement of endogenous glucocorticoids in this phenomenon. On the other hand, using cyclophosphamide and gemcitabine, we demonstrated that regulatory/suppressor CD4(+) CD25(+) forkhead boxP3(+) and GR-1(+) CD11b(+) cells do not play a major role in the establishment or the maintenance of endotoxin tolerance, a central mechanism for inducing an immunosuppression state.

Asunto(s)

RESUMEN

Multidetector CT scanners are now available in most hospitals; this technology makes it possible to perform cardiac studies. The technique depends on the technology, and certain points must be taken into consideration to improve the results of cardiac studies. We discuss four key points for ensuring high-quality multidetector CT studies. Under the heading patient preparation, we include deciding whether to use beta blockers, aspects related to the routine use of vasodilators, some guidelines for patient breath holding, etc. The next section discusses imaging acquisition, including when to use multisegmentation or even the possibility of prospective acquisition to reduce the dose of radiation. The third point deals with contrast administration to achieve good enhancement of the vessels. The last section reviews postprocessing techniques and comments on possible errors in 3D reconstructions or the need to render reconstructions of the entire thorax to rule out other diseases.

Asunto(s)

RESUMEN

OBJECTIVE: To describe the technique of US-guided shoulder arthrography using a pediatric needle (modified Valls- Melloni technique) and to assess its efficacy. MATERIAL AND METHODS: Descriptive study of articular puncture for 48 magnetic resonance imaging arthrographs of the shoulder in 48 consecutive patients. The puncture was performed by a radiologist without prior experience in the technique. We used an anterior approach to the shoulder, guiding the puncture using US according to the Valls-Melloni technique; however, we used a pediatric spinal needle (Yale spinal; 22G: 0.7 x 40 mm). The efficacy of the technique was evaluated using the following variables: time employed, number of attempts, extravasation of contrast outside the joint, pain reported by the patient (on a scale from 0 to 10), and immediate or late complications of the technique. RESULTS: The time required for the procedure was 15.2+/-2.6 min (mean+/-standard deviation). A single puncture sufficed in 45 patients (94%); two attempts were necessary in two patients (4%) and three in one patient (2%). Contrast extravasation outside the joint occurred only in two patients (4%). The mean pain reported was 3.6 points (confidence interval: 3.1-4). Three patients (6%) had a vasovagal reaction. No late complications were observed. CONCLUSION: US-guided shoulder arthrography using a pediatric spinal needle is fast, simple, and safe; it can be performed by any radiologist, even without prior experience in the technique.

Asunto(s)

RESUMEN

Objetivo. Describir la técnica de artrografía de hombro guiada con ecografía utilizando una aguja espinal infantil (técnica modificada de Valls y Melloni) y verificar su eficacia. Material y métodos. Estudio descriptivo de la técnica de punción articular en 48 artrografías de hombro mediante resonancia magnética, realizadas en 48 pacientes consecutivos. La punción la realizó un radiólogo sin experiencia previa en esta técnica. Se empleó un abordaje anterior del hombro guiando la punción mediante ecografía según la técnica de Valls y Melloni, pero utilizando una aguja espinal infantil (Yale spinal; 22G: 0,7 × 40 mm). La eficacia de la prueba se valoró mediante las variables: tiempo empleado, número de intentos, extravasación del contraste fuera de la articulación, dolor referido por el paciente (escala de 0 a 10) y complicaciones inmediatas o tardías de la técnica. Resultados. El tiempo del procedimiento fue de 15,2 ± 2,6 min (media ± desviación estándar). Se precisó una sola punción en 45 pacientes (94%); dos intentos en dos pacientes (4%) y tres en un paciente (2%). Solamente en dos pacientes existió extravasación del contraste fuera de la articulación (4%). La media del dolor referido fue de 3,6 puntos (intervalo de confianza: 3,1-4). Tres pacientes (6%) sufrieron una reacción vaso-vagal. No hubo complicaciones tardías. Conclusión. La artrografía de hombro guiada por ecografía y usando una aguja espinal infantil es una técnica rápida, sencilla y segura, que puede ser realizada por cualquier radiólogo, incluso sin experiencia previa en la técnica

Objective. To describe the technique of US-guided shoulder arthrography using a pediatric needle (modified Valls- Melloni technique) and to assess its efficacy. Material and methods. Descriptive study of articular puncture for 48 magnetic resonance imaging arthrographs of the shoulder in 48 consecutive patients. The puncture was performed by a radiologist without prior experience in the technique. We used an anterior approach to the shoulder, guiding the puncture using US according to the Valls-Melloni technique; however, we used a pediatric spinal needle (Yale spinal; 22G: 0.7 × 40 mm). The efficacy of the technique was evaluated using the following variables: time employed, number of attempts, extravasation of contrast outside the joint, pain reported by the patient (on a scale from 0 to 10), and immediate or late complications of the technique. Results. The time required for the procedure was 15.2 ± 2.6 min (mean ± standard deviation). A single puncture sufficed in 45 patients (94%); two attempts were necessary in two patients (4%) and three in one patient (2%). Contrast extravasation outside the joint occurred only in two patients (4%). The mean pain reported was 3.6 points (confidence interval: 3.1-4). Three patients (6%) had a vasovagal reaction. No late complications were observed. Conclusion. US-guided shoulder arthrography using a pediatric spinal needle is fast, simple, and safe; it can be performed by any radiologist, even without prior experience in the technique

Asunto(s)

RESUMEN

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infections are considered a public health problem in both developed and developing countries because of their increasing incidence and the severity of clinical presentation. Approximately 10% of infected patients develop complications such as haemolytic uraemic syndrome (HUS) characterized by acute renal failure, thrombocytopenia and haemolytic anaemia. The precise sequence of events leading to HUS is still understood incompletely. Because of the lack of a reproducible small animal model for EHEC infections, in vivo studies examining EHEC-host early interactions are limited and insufficient. The aim of this study was to characterize the weaned BALB/c mouse as a model of E. coli O157:H7 infection. In this paper we report that human Shiga toxin 2 (Stx2)-producing EHEC strains can adhere to the intestinal epithelium of weaned BALB/c mice, and produce local damage which leads to systemic disease and death in a percentage of infected mice. The lethality of the EHEC strain is closely age-dependent, and is related to the bacterial ability to colonize intestine and to produce Stx2. It can be concluded that the weaned BALB/c mouse can be used as a small animal model to study host early responses, and the role of bacterial pathogenic factors in the induction of systemic disease, thus providing a useful tool for the evaluation of therapeutic or vaccine approaches.

Asunto(s)

RESUMEN

Triatomine insects (Hemiptera) are the vectors of Chagas disease. Their cuticular surface is covered by a thin layer of lipids, mainly hydrocarbons, wax esters, fatty alcohols, and free or esterified fatty acids. These lipids play a major role in preventing a lethal desiccation, altering the absorption of chemicals and microorganism penetration, they also participate in chemical communication events. Lipid components are biosynthetically related, the synthesis of long chain and very long chain fatty acids was first shown in the integument of Triatoma infestans through the concerted action of fatty acid synthases (FAS's) and fatty acyl-CoA elongases. A final decarboxylation step produces the corresponding hydrocarbon. Capillary gas chromatography coupled to mass spectrometry analyses showed that cuticular hydrocarbons of Triatominae comprise saturated straight and methyl-branched chains, from 18 to more than 43 carbon atoms. Odd-chain hydrocarbons, mostly from 27 to 33 carbons, are the major straight chains. Different isomers of mono, di, tri, and tetramethylcomponents, mostly from 29 to 39 atoms in the carbon skeleton, account for the major methyl-branched hydrocarbons. The presence, absence, and relative quantities of these hydrocarbons represent characters for their chemical phenotype, and are useful for differentiating genera, species and populations. In this review, we will discuss the metabolic pathways involved in hydrocarbon formation, and their structure, together with their role in insect survival. We will also review the utility of cuticular hydrocarbon fingerprints in chemotaxonomy.

Asunto(s)

RESUMEN

It has been demonstrated that infections due to Shiga toxins (Stx) producing Escherichia coli are the main cause of the haemolytic uraemic syndrome (HUS). However, the contribution of the inflammatory response in the pathogenesis of the disease has also been well established. Neutrophils (PMN) represent a central component of inflammation during infections, and patients with high peripheral PMN counts at presentation have a poor prognosis. The mouse model of HUS, by intravenous injection of pure Stx type 2 (Stx2), reproduces human neutrophilia and allows the study of early events in the course of Stx2-induced pathophysiological mechanisms. The aim of this study was to address the contribution of PMN on Stx2 toxicity in a murine model of HUS, by evaluating the survival and renal damage in mice in which the granulocytic population was depleted. We found that the absence of PMN reduced Stx2-induced lethal effects and renal damage. We also investigated the mechanisms underlying Stx2-induced neutrophilia, studying the influence of Stx2 on myelopoyesis, on the emergence of cells from the bone marrow and on the in vivo migration into tissues. Stx2 administration led to an accelerated release of bone marrow cells, which egress at an earlier stage of maturation, together with an increase in the proliferation of myeloid progenitors. Moreover, Stx2-treated mice exhibited a lower migratory capacity to a local inflammatory site. In conclusion, PMN are essential in the pathogenesis of HUS and neutrophilia is not merely an epiphenomenon, but contributes to Stx2-damaging mechanism by potentiating Stx2 toxicity.

Asunto(s)

RESUMEN

The air-surface exchange of mercury (Hg) was measured, using a dynamic polycarbonate flux chamber, for soils with low or "background" Hg concentrations (<0.1 mg/kg) at eleven locations across the contiguous United States. Sampling locations included agricultural, desert, grassland, mixed and pine forest ecosystems (n=1326 soil flux measurements at 46 individual sites). An overall soil Hg flux of 0.9+/-0.2 ng/m2/h for these background soils was obtained by averaging the means for the different locations. Soil Hg fluxes were significantly lower in dark conditions than in the light for all but the grassland sites. Mean inlet air Hg concentrations were 1.0+/-0.1 ng/m3 in the dark and 1.3+/-0.2 ng/m3 in the light. Soil temperature inside and outside of the chamber, air temperature, relative humidity, and irradiance were measured concurrently with soil Hg flux. Soil-air Hg exchange was weakly predicted by environmental variables (R2 from 0.07 to 0.52). For a single location, flux was better correlated with soil moisture than other measured environmental parameters, suggesting that soil moisture might be an important driver for Hg emissions from background soils. In addition, based on data collected we suggest some quality control measures for use of Tekran 2537A analyzers when measuring low mercury fluxes. Using basic scaling procedures, we roughly estimate that natural emissions from soils in the contiguous U.S. release approximately 100 Mg/yr of Hg to the atmosphere.

Asunto(s)

RESUMEN

The central role of the immune system is the preservation of the health against several pathogenic microbes and injury agents. However, on special conditions defensive mechanisms triggered towards the foreign agent can damage the host. Clinical and experimental evidence indicate that inflammatory reaction triggered by the main components of Shiga toxin (Stx)-producing Escherichia coil (STEC), participate in the evolution to the complete form of HUS. When children are diagnosed of HUS, they present evidence that have suffered a very strong and early inflammatory response. These features include: the presence of a marked neutrophilia, the polymorfonuclear leucocytes (PMN) are "deactivated or exhausted" and the monocytes are differentiated towards an inflammatory phenotype (CD14-reduced and CD16-enhanced membrane expression). In addition, HUS-patients show a marked reduction in the absolute and relative number of leucocytes carrying the receptor (CX3CR1) for the chemokine "Fractalkine" (FKN, CX3CL1), which are the classic monocytes and Natural Killer cells (NK). All these cells express a high cytotoxic potencial. The chemokine FKN is expressed in endothelial and epithelial renal cells, and is involved in the pathogenic mechanism of different nephropathies. Noteworthy, we found a significant correlation between the severity of the renal damage (as days of anuria) and the alterations described above. Finally, the protective role of specific immune response, mainly through the antibody production with Stx-neutralizing capacity, is discussed.

Asunto(s)

RESUMEN

The central role of the immune system is the preservation of the health against several pathogenic microbes and injury agents. However, on special conditions defensive mechanisms triggered towards the foreign agent can damage the host. Clinical and experimental evidence indicate that inflammatory reaction triggered by the main components of Shiga toxin (Stx)-producing Escherichia coil (STEC), participate in the evolution to the complete form of HUS. When children are diagnosed of HUS, they present evidence that have suffered a very strong and early inflammatory response. These features include: the presence of a marked neutrophilia, the polymorfonuclear leucocytes (PMN) are "deactivated or exhausted" and the monocytes are differentiated towards an inflammatory phenotype (CD14-reduced and CD16-enhanced membrane expression). In addition, HUS-patients show a marked reduction in the absolute and relative number of leucocytes carrying the receptor (CX3CR1) for the chemokine "Fractalkine" (FKN, CX3CL1), which are the classic monocytes and Natural Killer cells (NK). All these cells express a high cytotoxic potencial. The chemokine FKN is expressed in endothelial and epithelial renal cells, and is involved in the pathogenic mechanism of different nephropathies. Noteworthy, we found a significant correlation between the severity of the renal damage (as days of anuria) and the alterations described above. Finally, the protective role of specific immune response, mainly through the antibody production with Stx-neutralizing capacity, is discussed.(AU)

Asunto(s)

RESUMEN

We report a case of necrotizing granulomatous vasculitis in the spermatic cord in a 35-year-old man with an antecedent of brain stroke 3 years before. The clinical manifestation was as a painless left scrotal mass. The diagnosis was established by histological examination of the spermatic cord. We discuss the physical findings, radiological features and pathological findings, reviewing the literature for previous similar cases.

Asunto(s)

RESUMEN

Haemolytic uraemic syndrome (HUS) is caused by Shiga-toxin-producing Escherichia coli (STEC). Although, Shiga toxin type 2 (Stx2) is responsible for the renal pathogenesis observed in patients, the inflammatory response, including cytokines and polymorphonuclear neutrophils (PMN), plays a key role in the development of HUS. Previously, we demonstrated that Stx2 injection generates an anti-inflammatory reaction characterized by endogenous glucocorticoid (GC) secretion, which attenuates HUS severity in mice. Here, we analysed the effects of Stx2 on the pathogenic function of PMN and the potential role of endogenous GC to limit PMN activation during HUS development in a murine model. For this purpose we assessed the functional activity of isolated PMN after in vivo treatment with Stx2 alone or in simultaneous treatment with Ru486 (GC receptor antagonist). We found that Stx2 increased the generation of reactive oxygen intermediates (ROI) under phobol-myristate-acetate (PMA) stimulation and that the simultaneous treatment with Ru486 strengthened this effect. Conversely, both treatments significantly inhibited in vitro phagocytosis. Furthermore, Stx2 augmented in vitro PMN adhesion to fibrinogen (FGN) and bovine serum albumin (BSA) but not to collagen type I (CTI). Stx2 + Ru486 caused enhanced adhesion to BSA and CTI compared to Stx2. Whereas Stx2 significantly increased migration towards N-formyl-methionyl-leucyl-phenylalanine (fMLP), Stx2 + Ru486 treatment enhanced and accelerated this process. The percentage of apoptotic PMN from Stx2-treated mice was higher compared with controls, but equal to Stx2 + Ru486 treated mice. We conclude that Stx2 activates PMN and that the absence of endogenous GC enhances this activation suggesting that endogenous GC can, at least partially, counteract PMN inflammatory functions.

Asunto(s)

RESUMEN

Twenty geldings (five groups; similar age and BW) were used in a completely randomized design experiment to determine effects of grain supplementation of an alfalfa-cube diet on apparent nutrient digestibility and hindgut fermentation. The geldings were housed individually, fed their diets in two equal meals (0600 and 1800), and adapted to five dietary treatments over 6 wk. The treatments were alfalfa cubes (1% of BW; DM basis) without (control) or with one of four rolled cereal grains (i.e., barley, corn, naked oats, or oats) to provide a target level of 0.4% of BW as total nonstructural carbohydrates (TNC). Due to acute laminitis, three geldings (one in the control group and two in the barley group) were excluded. Because of this and multiple incidents of gas colic, TNC level was decreased to 0.2% of BW to ensure the geldings' health throughout the adaptation (7 d) and sample collection (5 d) periods. Grain intakes varied (P < 0.05) and reflected the different TNC concentrations. Apparent digestibilities of DM, OM, CP, NDF, ADF, and cellulose were not affected (P > 0.05) by grain supplementation and averaged 63.2, 63.1, 79.5, 42.7, 39.9, and 50.3%, respectively. Regardless of the source, grain supplementation increased (P < 0.05) apparent digestibility of TNC (from 85.6 to 94.6%) and decreased (P < 0.05) fecal pH (from 7.04 to 6.74). Fecal concentrations of total VFA (mg/g of DM) were greatest for the barley and naked oats diets (averaging 11.73), intermediate for the oats diet (8.00), and least for the control and corn diets (averaging 5.00; P < 0.05). Fecal concentrations of lactate (microg/g of DM) were greatest for the barley diet (254), intermediate for the oats diet (138), and least for the remaining diets (averaging 100; P < 0.05). Fecal concentrations of NH3 N (mg/g of DM) were greatest for the naked oats diet (1.68), intermediate for the barley and oats diets (averaging 0.86), and least for the remaining diets (averaging 0.63; P < 0.05). Serum concentration of lactate was 46% higher (P < 0.05) for the control than for the grain diets (averaging 0.05 mg/100 mL). Feeding barley, corn, naked oats, and oats contributed to 13, 15, 8, and 20% higher (P < 0.05) serum NH3 N concentrations than the control diet (0.25 mg/100 mL). Higher (P < 0.05) serum concentrations of urea N (mg/100 mL) were detected for the control, barley, and naked oats diets (averaging 25.28) than for the corn or oats diets (averaging 22.21). Results suggest that horses consuming alfalfa cubes could be supplemented with rolled barley, corn, naked oats, or oats at levels not exceeding 0.2% of BW as TNC without affecting nutrient digestion or overall health negatively.

Asunto(s)

RESUMEN

We report the appearance of three cases of Leydig cell tumours on MRI. This imaging method showed well-defined and peripheral intratesticular tumours displaying marked and homogeneous enhancement when contrast medium was used. This latter finding was only observed in Leydig cell tumours when they were compared in a series of 104 patients with different scrotal pathologies.

Asunto(s)

RESUMEN

The interaction between receptors for the Fc portion of IgG (FcgammaRs) from monocytes/macrophages and immune complexes (IC) triggers regulatory and effector functions. Recently, we have demonstrated that IC exert a drastic inhibition of basal and IFN-gamma-induced expression of MHC class II on human monocytes. Taking into account that the regulation of MHC class II molecules is a crucial event in the immune response, in this report we extend our previous studies analysing the effect of STAT-1 phosphorylation in the down-regulatory process, the fate of the intracellular pool of MHC class II molecules and the effect of complement on MHC class II down-regulation induced by IC. We also studied the effect of IC on the expression of MHC class II (I-A(d)) in macrophages using a mouse model of chronic inflammation. We demonstrate that IC induce a depletion not only on surface expressed but also on intracellular MHC class II content and that IC-induced down-regulation of MHC class II is not mediated by the inhibition of STAT-1 phosphorylation. On the other hand, the effect of IC is not specific for the down-regulation of MHC class II, for it could be restricted to other molecules involved in inflammatory processes. Our experiments also show that the activation of the complement system could be a crucial step on the regulation of the effect of IC on MHC class II expression. In agreement with our in vitro experiments using human monocytes, IC treatment reduces the expression of MHC class II in a mouse model of chronic inflammation.

Asunto(s)

RESUMEN

The concept that during an immune challenge the release of glucocorticoids (GC) provides feedback inhibition on evolving immune responses has been drawn primarily from studies of autoimmune and/or inflammatory processes in animal models. The epidemic form of haemolytic uraemic syndrome (HUS) occurs secondary to infection with Gram-negative bacteria that produce Shiga toxin (Stx). Although Stx binding to the specific receptors present on renal tissue is the primary pathogenic mechanism, inflammatory or immune interactions are necessary for the development of the complete form of HUS. The aim of this study was to investigate the influence of endogenous GC on Stx-toxicity in a mouse model. Stx2 was injected into GC-deprived mice and survival rate, renal damage and serum urea levels were evaluated. Plasma corticosterone and cytosolic GC receptor (GR) concentration were also determined at multiple intervals post-Stx2 treatment. Higher sensitivity to Stx2 was observed in mice lacking endogenous GC, evidenced by an increase in mortality rates, circulating urea levels and renal histological damage. Moreover, Stx2 injection was associated with a transient but significant rise in corticosterone secretion. Interestingly, 24 h after Stx inoculation significant increases in total GR were detected in circulating neutrophils. These results indicate that interactions between the neuroendocrine and immune systems can modulate the level of damage significantly during a bacterial infection.

Asunto(s)