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Biomedical subjects

J Schwarze

Publications and source records attributed to J Schwarze.

At least 19 recordsLinked to original sources
PubMed2005

Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness.

BACKGROUND: Recent epidemiological studies have shown that growing up on a traditional farm provides protection from the development of allergic disorders such as hay fever and allergic asthma. We present experimental evidence that substances providing protection from the development of allergic diseases can be extracted from dust collected in stables of animal farms. METHODS: Stable dust was collected from 30 randomly selected farms located in rural regions of the Alps (Austria, Germany and Switzerland). The dust was homogenised with glass beads and extracted with physiological sodium chloride solution. This extract was used to modulate immune response in a well established mouse model of allergic asthma. RESULTS: Treatment of mice by inhalation of stable dust extract during sensitisation to ovalbumin inhibited the development of airway hyperresponsiveness and airway eosinophilia upon challenge, as well as the production of interleukin 5 by splenocytes and of antigen specific IgG(1) and IgE. Dust extract also suppressed the generation of human dendritic cells in vitro. The biological activity of the dust extract was not exclusively mediated by lipopolysaccharide. CONCLUSIONS: Stable dust from animal farms contains strong immune modulating substances. These substances can interfere with the development of both cellular and humoral immunity against allergens, thus suppressing allergen sensitisation, airway inflammation, and airway hyperresponsiveness in a murine model of allergic asthma.

Allergens↗
PubMed2004

Enhanced virulence, airway inflammation and impaired lung function induced by respiratory syncytial virus deficient in secreted G protein.

BACKGROUND: Respiratory syncytial virus (RSV) infection can cause bronchial hyperresponsiveness and asthma exacerbations. In mice it results in airway inflammation and airway hyperresponsiveness. Since viral factors influencing these responses are not well defined, a study was undertaken to investigate the role of secreted G protein of human RSV in determining virulence, inflammatory responses, and changes in lung function. METHODS: BALB/c mice were infected with a spontaneous mutant of RSV deficient in secreted G protein (RSV-DeltasG) or with wild type RSV (RSV-WT). Viral titres, numbers of pulmonary inflammatory cells, and concentrations of interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 in bronchoalveolar lavage (BAL) fluid were determined. Airway function was assessed at baseline and following methacholine provocation using barometric whole body plethysmography. RESULT: Following infection with RSV-DeltasG, viral titres were increased 50-fold compared with RSV-WT. Influx of eosinophils and macrophages to the lung and concentrations of IFN-gamma and IL-10 in BAL fluid were also significantly higher following infection with RSV-DeltasG. Airway function, both at baseline and after methacholine provocation, was significantly decreased following infection with RSV-DeltasG compared with RSV-WT. CONCLUSION: Secreted G protein is likely to be a regulatory factor in RSV infection limiting infectivity of the virus, inflammatory responses in the lungs, and reduction in lung function.

Animals↗
PubMed2003

Blockade of HMG-CoA reductase activity causes changes in microtubule-stabilizing protein tau via suppression of geranylgeranylpyrophosphate formation: implications for Alzheimer's disease.

Histopathologically, Alzheimer's disease is characterized by plaques and tangles that develop progressively over time. Experimental data described a statin-induced decrease in beta-amyloid production, a major constituent of the plaques. Others reported data on statin-mediated changes in neuronal survival and cytoskeleton, including the microtubule-associated protein tau, a major constituent of the tangles. However, these latter reports remain contradictory. To clarify and extend our knowledge on the effect of statin on the cytoskeleton, we challenged rat primary neuron cultures by lovastatin and determined the metabolite that is critical for structural integrity and survival of neurons. During the blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the neuritic network was affected and eventually was completely destroyed. This process was not part of the execution phase of apoptosis and was marked by alterations in the microfilament and microtubule system. The distribution and phosphorylation of protein tau changed. Immunoblot analysis and indirect immunofluorescence revealed a transient increase in tau phosphorylation, which ceased during the execution of apoptosis. All of these effects could be linked to the lack of the geranylgeranylpyrophosphate intermediate. Inhibition of the geranylgeranylation of Rho family GTPases (geranylgeranyl-transferase I) evoked similar changes in neurons. These data and our findings that statin treatment reduced the membrane-bound fraction of RhoA-GTPase in neurons suggest that reduced levels of functional small G proteins are responsible for the observed effects. Our data demonstrate that lovastatin concentrations able to suppress not only cholesterol but also geranylgeranylpyrophosphate formation may evoke phosphorylation of tau reminiscent of preclinical early stages of Alzheimer's disease and, when prolonged, apoptosis.

Alzheimer Disease↗
PubMed2002

Infection of murine precision cut lung slices (PCLS) with respiratory syncytial virus (RSV) and chlamydophila pneumoniae using the Krumdieck technique.

The Krumdieck technique allows the investigation of the so-called precision cut lung slices (PCLS) with a special microtome. It is thus possible to evaluate morphologic changes over a longer period of time using only a small group of animals. Chlamydophila pneumoniae (Cp) and respiratory syncytial virus (RSV) proved to be important causes of pneumonia, rhinitis and exacerbations of asthma bronchiale, as well as of lower respiratory tract infections in young children. PCLS should be tested for their suitability as an in vitro model for these infections. The PCLS were infected with Cp and RSV over different periods of time. Investigations were carried out by light and transmission electron microscopy (TEM). Furthermore, immunofluorescence (IF) studies with antibodies against bacterial or viral proteins and cell-specific markers were done using confocal laser scanning microscopy (CLSM). Non-infected and infected PCLS showed a well-preserved morphology up to 72 hours. After short infection intervals, typical inclusions of Cp or RSV were detected in vacuoles of different cell types. Infection and cell types could be verified using IF. Cytopathic effects were not prominent. Ciliary beat was detectable up to 96 hours after infection. This in vitro technique offers the possibility of studying mechanisms and effects of bacterial and viral infections on viable tissue complexes.

Animals↗
PubMed2002

Respiratory viral infections as promoters of allergic sensitization and asthma in animal models.

Respiratory virus infections can trigger exacerbations of asthma and may also contribute to allergic sensitization to aeroallergens and the development of asthma. Conversely, atopy may predispose to more severe virus-induced airway disease. The animal models reviewed in this article support the hypothesis that respiratory virus infections can promote allergic sensitization and the development of asthma. Respiratory viruses can prevent induction of tolerance and enhance sensitization to inhaled allergens resulting in increased airway inflammation and airway hyperresponsiveness. Probable mechanisms involved in this enhanced sensitization are increased permeability of the airway mucosa to allergens and recruitment of dendritic cells to the respiratory epithelium during acute infection. Factors involved in augmenting the consequences of allergic airway sensitization appear to be T-cells, especially CD8+ T-cells as regulators of this process, interleukin-5 as a pivotal cytokine for eosinophilic airway inflammation and eosinophils themselves as effector cells triggering airway hyperresponsiveness. Depending on the timing of allergen exposure, respiratory virus infections which elicit a significant type 1 T-helper cell cytokine response may also downregulate allergic sensitization. Respiratory virus infections in animals previously sensitized to aeroallergens result in prolonged increases in inflammation and airway responsiveness, indicating that critical interactions between immune responses to allergen sensitization and the responses to infection can lead to more severe disease. Taken together, animal models have proved valuable in generating a number of plausible pathogenetic concepts, and can be used to address a host of unresolved questions regarding the immunology of respiratory virus infections, allergic sensitization and asthma.

Allergens↗
PubMed2000

The role of viruses in development or exacerbation of atopic asthma.

Respiratory viral infections in early childhood have been linked to the development of persistent wheezing and asthma. Epidemiologic data indicate that, for the majority of children, virus-induced wheezing is a self-limited condition, with no long-term consequences. For a substantial minority, however, virus-induced wheezing is associated with persistent asthma and the potential for enhanced allergic sensitization. For the most part, this subset of patients is genetically predisposed; they are atopic children in whom respiratory viral infections trigger the early development of asthma by mechanisms that have not been fully elucidated. Both inflammatory and noninflammatory mechanisms may be involved. It does not appear that viral infection per se in early life is responsible for the induction of atopic asthma. Data from animal models provide support for the concept that enhanced allergic sensitization caused by increased uptake of allergen during infection may play a critical role, as well as T-cell-mediated immune responses to viral infection, which may favor eosinophilic inflammatory responses and the development of altered airway function to inhaled methacholine. Recent advances in our understanding of the interactions between respiratory viruses and the development of reactive airway disease offer new possibilities for preventive treatment in children at risk for developing persistent wheezing and asthma exacerbation as a result of viral infection.

Animals↗
PubMed2000

Critical roles for interleukin-4 and interleukin-5 during respiratory syncytial virus infection in the development of airway hyperresponsiveness after airway sensitization.

In mice, respiratory syncytial virus (RSV) infection can enhance the consequences of allergic airway sensitization, resulting in lung eosinophilia and the development of airway hyperresponsiveness (AHR) to inhaled methacholine (MCh). To delineate a role for interleukin-5 (IL-5), interleukin-4 (IL-4), and interferon gamma (IFN-gamma) in mediating the effects of RSV infection on subsequent allergic sensitization, we treated BALB/c mice with anti-IL-5 during acute RSV infection but not during subsequent exposure to ovalbumin (OVA). IL-5-deficient and IL-4-deficient mice were also treated with IL-5 either during acute RSV infection or during the sensitization period. Airway responsiveness to inhaled MCh was assessed and numbers of lung eosinophils were monitored. Anti-IL-5 treatment during RSV infection reduced AHR and lung eosinophilia after subsequent exposure to allergen. In IL-5-deficient or IL-4-deficient mice lung eosinophilia and AHR after RSV infection and allergen exposure were also markedly reduced. IL-5 administration during RSV infection restored the responses to allergen in both IL-5- and IL-4-deficient mice. However, IL-5 administration only during sensitization restored these responses in IL-4-deficient but not in IL-5-deficient animals. IFN-gamma-deficient mice developed AHR and some lung eosinophilia after allergen exposure alone and when RSV infection preceded allergen, these responses were enhanced. We conclude that both IL-5, particularly during acute infection, and IL-4 are critical in mediating the effects of RSV infection on allergic airway sensitization, resulting in the development of AHR and lung eosinophilia.

Animals↗
PubMed2000

Type 4 phosphodiesterase inhibitors attenuate respiratory syncytial virus-induced airway hyper-responsiveness and lung eosinophilia.

Viral respiratory infections are considered one of the triggers of exacerbations of asthma. In a model of virus-induced airway hyper-responsiveness (AHR), mice infected with human respiratory syncytial virus (RSV) were shown to develop AHR accompanied by lung eosinophilia. Inhibitors of cyclic nucleotide phosphodiesterase (PDE) have been shown to affect airway responsiveness and pulmonary allergic inflammation. In this study, we assessed the effects of type 4 PDE (PDE4) inhibitors on AHR following RSV infection and compared them with a PDE3 inhibitor. In mice infected by intranasal inoculation of RSV, treatment with the PDE4 inhibitor rolipram or Ro-20-1724 reduced both AHR and the eosinophil infiltration of the airways. In contrast, the PDE3 inhibitor, milrinone, did not influence airway responsiveness or eosinophilic inflammation. These results demonstrate that PDE4 inhibitors can modulate RSV-induced AHR and lung eosinophilia and indicate that they have a potential role in treating exacerbations of asthma triggered by viral infection.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

[Peliosis hepatis: problems of differential diagnosis].

Peliosis hepatis is a syndrome manly known to internists and pathologists. It is described as roundish blood cysts up to 1 cm large to the found in the hepatic parenchyma and correlated to the hepatic sinusoids. The pathogenesis is still unclear. The presumably essential disturbance of the structure of the reticular fibres is etiologically associated with anabolic and androgenic steroid therapy. Peliosis hepatis is pathognomonic for treatment with contraceptives and for severe chronic diseases, as tuberculosis or tumour. Little is known of therapeutic methods on the diagnostic of peliosis alterations in the liver. As peliosis-type hepatic lesions are apt to involution, it is generally recommended just to wait and see, with controlling examinations for imaging diagnostics. A case is described where a female patient, aged 42, otherwise healthy, came to see the doctor for obscure pain in the upper abdomen. Sonography of the upper abdomen indicated multiple lesions. The diagnostic method is described taking into account possible malign differential diagnoses or associated malign results which finally lead to partial resection of the liver.

Abdominal Pain↗
PubMed1999

Transfer of the enhancing effect of respiratory syncytial virus infection on subsequent allergic airway sensitization by T lymphocytes.

In mice, respiratory syncytial virus (RSV) infection enhances allergic airway sensitization, resulting in lung eosinophilia and in airway hyperresponsiveness (AHR). The mechanisms by which RSV contributes to development of asthma and its effects on allergic airway sensitization in mice are not known. We tested whether these consequences of RSV infection can be adoptively transferred by T cells and whether depletion of T cell subsets prevents the effects of RSV infection on subsequent airway sensitization. Mononuclear cells, T lymphocytes, or CD4 or CD8 T cells from peribronchial lymph nodes (PBLN) of RSV-infected mice were transferred into naive BALB/c mice which were then exposed to OVA via the airways. Additionally, RSV-infected mice were depleted of CD4 or CD8 T cells following acute RSV infection but prior to airway sensitization. Following sensitization, airway responsiveness to inhaled methacholine, numbers of lung eosinophils, and levels of IFN-gamma, IL-4, and IL-5 in PBLN cell cultures were monitored. Transfer of T cells from RSV-infected mice resulted in increased eosinophil influx into the lungs, increased IL-5 production, and development of AHR following airway sensitization to allergen. Transfer of CD8 but not CD4 T cells from the PBLN of RSV-infected mice also resulted in AHR following 10 days of OVA exposure. Further, depletion of CD8 T cells prevented these consequences of RSV infection while CD4 T cell depletion reduced them. We conclude that T cells, in particular CD8 T cells, are critical in mediating RSV-induced development of lung eosinophilia and AHR following allergic airway sensitization.

Adoptive Transfer↗
PubMed1999

Systemic and local interferon gamma gene delivery to the lungs for treatment of allergen-induced airway hyperresponsiveness in mice.

Allergen-induced airway hyperresponsiveness, an animal model of asthma in humans, may respond to immunotherapy with Th1 cytokines. For example, local administration of recombinant IL-12 or IFN-gamma, or intratracheal delivery of the genes for these cytokines, has been shown to reduce the severity of allergen-induced airway hyperresponsiveness (AHR) in rodent models. We reasoned that systemic cytokine gene delivery to the lungs by intravenous injection of lipid-DNA complexes might also be an effective approach to treatment of allergen-induced AHR. Therefore, the effects of either systemic or local pulmonary IFN-gamma gene delivery were evaluated in mice with allergen-induced AHR. The effects of treatment on AHR, airway eosinophilia and cytokine production, and serum IgE concentrations were evaluated in mice that were first sensitized to ovalbumin and then subjected to aerosol ovalbumin challenge. Intravenous IFN-gamma gene delivery significantly inhibited development of AHR and airway eosinophilia and decreased serum IgE levels, compared with control mice or mice treated with noncoding DNA. Intratracheal IFN-gamma gene delivery also significantly inhibited AHR and airway eosinophilia, but did not affect serum IgE levels. Treatment with recombinant IFN-gamma was much less effective than IFN-gamma gene delivery by either route. We conclude that either systemic or local pulmonary delivery of a Th1 cytokine gene such as IFN-gamma may be an effective approach for treatment of allergen-induced asthma.

Allergens↗
PubMed1999

CD8 T cells are essential in the development of respiratory syncytial virus-induced lung eosinophilia and airway hyperresponsiveness.

Viral respiratory infections can cause bronchial hyperresponsiveness and exacerbate asthma. In mice, respiratory syncytial virus (RSV) infection results in airway hyperresponsiveness (AHR) and eosinophil influx into the airways. The immune cell requirements for these responses to RSV infection are not well defined. To delineate the role of CD8 T cells in the development of RSV-induced AHR and lung eosinophilia, we tested the ability of mice depleted of CD8 T cells to develop these symptoms of RSV infection. BALB/c mice were depleted of CD8 T cells using anti-CD8 Ab treatment before intranasal administration of infectious RSV. Six days postinfection, airway responsiveness to inhaled methacholine was assessed by barometric body plethysmography, and numbers of lung eosinophils and levels of IFN-gamma, IL-4, and IL-5 in bronchoalveolar lavage fluid were monitored. RSV infection resulted in airway eosinophilia and AHR in control mice, but not in CD8-depleted animals. Further, whereas RSV-infected mice secreted increased amounts of IL-5 into the airways as compared with noninfected controls, no IL-5 was detectable in both bronchoalveolar lavage fluid and culture supernatants from CD8-depleted animals. Treatment of CD8-depleted mice with IL-5 fully restored both lung eosinophilia and AHR. We conclude that CD8 T cells are essential for the influx of eosinophils into the lung and the development of AHR in response to RSV infection.

Acute Disease↗
PubMed1999

IL-5 and eosinophils are essential for the development of airway hyperresponsiveness following acute respiratory syncytial virus infection.

Viral respiratory infections can cause bronchial hyperresponsiveness and exacerbate asthma. In mice, respiratory syncytial virus (RSV) infection, which induces an immune response dominated by IFN-gamma, results in airway hyperresponsiveness (AHR) and eosinophil influx into the airways, both of which are prevented by pretreatment with anti-IL-5 Ab. To delineate the role of IL-5, IL-4, and IFN-gamma in the development of RSV-induced AHR and lung eosinophilia, we tested the ability of mice deficient in each of these cytokines to develop these symptoms of RSV infection. Mice deficient in either IL-5, IL-4, or IFN-gamma were administered infectious RSV intranasally, and 6 days later, airway responsiveness to inhaled methacholine was assessed by barometric body plethysmography, and numbers of lung eosinophils and production of IFN-gamma, IL-4, and IL-5 by mononuclear cells from peribronchial lymph nodes were monitored. RSV infection resulted in airway eosinophilia and AHR in both IL-4- and IFN-gamma-deficient mice, but not in IL-5-deficient mice. Reconstitution of IL-5-deficient mice with IL-5 restored these responses and enhanced the responses in IL-4-deficient mice. Anti-VLA-4 (very late Ag-4) treatment prevented lung eosinophilia and AHR following RSV infection and IL-5 reconstitution. We conclude that in response to RSV, IL-5 is essential for the influx of eosinophils into the lung and that eosinophils in turn are critical for the development of AHR. IFN-gamma and IL-4 are not essential for these responses to RSV infection.

Acute Disease↗
PubMed1999

Negative regulation of airway responsiveness that is dependent on gammadelta T cells and independent of alphabeta T cells.

The mechanisms regulating airway function are complex and still poorly understood. In diseases such as asthma, involvement of immune-dependent mechanisms has been suggested in causing changes in airway responsiveness to bronchoconstrictors. We now demonstrate that gammadelta T cells can regulate airway function in an alphabeta T cell-independent manner, identifying them as important cells in pulmonary homeostasis. This function of gammadelta T cells differs from previously described immune-dependent mechanisms and may reflect their interaction with innate systems of host defense.

Animals↗
PubMed1999

Anti-interleukin 5 but not anti-IgE prevents airway inflammation and airway hyperresponsiveness.

The role of IL-5 and allergen-specific IgE in the development of eosinophilic airway inflammation and airway hyperresponsiveness (AHR) was investigated in a murine model. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection on Days 1 and 14, followed by airway challenge with OVA on Days 28 and 29. Anti-IL-5 (TRFK-5) or anti-IgE (antibody 1-5) was administered before each airway challenge. Sensitized and challenged mice developed increased OVA-specific IgE serum levels, Th2 cytokine production by peribronchial lymph node (PBLN) cells, increased numbers of eosinophils (predominantly located in the peribronchial regions of the lungs), and increased airway responsiveness to methacholine (MCh). Anti-IgE treatment significantly decreased serum anti-OVA IgE levels and prevented the development of anaphylaxis but failed to affect T cell function, eosinophil airway infiltration, and AHR in sensitized and challenged mice. In contrast, treatment with anti-IL-5 antibody did not affect B cell (Ig serum levels), T cell (cytokine production), or mast cell function (immediate cutaneous reactivity) but completely inhibited development of eosinophilic lung inflammation and AHR. These data identify IL-5-mediated eosinophilia as a major target for development of AHR in this model, with little effect resulting from neutralization of IgE.

Analysis of Variance↗