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  • 1
    Electronic Resource
    Electronic Resource
    Effects of Interferon-γ and Tumour Necrosis Factor-α on CD95/Fas Ligand-Mediated Apoptosis in Human Blood Eosinophils (2000)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 51 (2000), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Many cells, including eosinophils, express CD95 (Fas), a surface receptor that mediates apoptosis when ligated by specific antibodies or its natural ligand, Fas ligand (FasL). As apoptosis may play an important role in the regulation of tissue eosinophilia, factors that modulate eosinophil sensitivity to apoptosis are of great interest. It has previously been shown that interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) together increase CD95 surface expression on eosinophils. However, the functional consequences of this increase in CD95 expression have not been demonstrated in detail. We therefore investigated whether the increase in CD95 expression mediated by IFN-γ/TNF-α indeed translates into increased, FasL-mediated apoptosis of eosinophils. For this purpose, purified eosinophils from normal donors were incubated with different concentrations of FasL and induction of apoptosis was assessed by annexin-V/propidium iodide assay. Unlike Jurkat cells, which became apoptotic within 2 h after incubation with FasL, an increase in eosinophil apoptosis could first be dedicated after 6 h incubation with FasL. Prestimulation with IFN-γ/TNF-α for 24 h significantly enhanced FasL-induced apoptosis in eosinophils. This increase in CD95/FasL-mediated apoptosis was correlated with an IFN-γ/TNF-α-mediated increase in CD95 expression. From these findings we conclude that the combination of IFN-γ and TNF-α enhances CD95 expression, which results in an increase in FasL-mediated apoptosis of eosinophils in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2000.00645.x
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibition of HLA-DR Expression on Activated Human Blood Eosinophils by Transforming Growth Factor-β1 (1998)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 48 (1998), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Peripheral blood, bronchoalveolar lavage and sputum eosinophils of patients with asthma but not peripheral blood eosinophils from normal controls have been shown to express human leucocyte antigen (HLA)-DR on their cell surface. Cytokines implicated in the activation of eosinophils, such as interleukin (IL)-3 and granulocyte–macrophage colony-stimulating factor (GM-CSF), can up-regulate HLA-DR expression. However, little is known about antagonistic factors that might down-regulate HLA-DR expression on eosinophils. In this study we investigated whether transforming growth factor-β (TGF-β), which has been shown to reduce survival of activated eosinophils, can also modulate HLA-DR expression on eosinophils. For this purpose, isolated peripheral blood eosinophils were stimulated with IL-3 and GM-CSF for 24 h and HLA-DR expression was measured by flow cytometry. We found that while isolated eosinophils expressed low levels of surface HLA-DR, incubation with GM-CSF and IL-3 increased HLA-DR expression on eosinophils. TGF-β alone did not change HLA-DR expression on isolated eosinophils. However, co-incubation of eosinophils with TGF-β and either GM-CSF or IL-3 significantly decreased HLA-DR expression compared to eosinophils incubated with either GM-CSF or IL-3 alone and this was not reversed by addition of IL-5. This effect of TGF-β on IL-3-induced HLA-DR expression was attenuated dose-dependently in the presence of monoclonal anti-TGF-β antibodies. Our results suggest that TGF-β can reduce cytokine-induced HLA-DR expression on eosinophils and could thus influence eosinophil activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1998.00446.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of TGF-β on Eosinophil Chemotaxis (1998)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 47 (1998), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Transforming growth factor-β (TGF-β), which can decrease the effects of interleukin (IL)-3, IL-5 and granulocyte–macrophage colony-stimulating factor (GM-CSF) on eosinophil viability, has been shown to be chemotactic for neutrophils. However, there is little information on its effects on eosinophil chemotaxis. Because TGF-β has recently been found in increased concentrations in asthmatic sputum, we investigated whether TGF-β could influence eosinophil migration and eosinophil viability. Purified eosinophils from normal donors were incubated with increasing concentrations of TGF-β. Chemotaxis was measured with a modified Boyden chamber technique. In addition, eosinophils were incubated for 96 h with either IL-3, IL-5 or GM-CSF (1 ng/ml) together with increasing concentrations of TGF-β. Eosinophil viability was then determined with propidium jodide and flowcytometry. Eosinophil chemotaxis was significantly increased in the presence of TGF-β in concentrations between 10−9 and 10−4 μg/ml. The optimal concentration of TGF-β in this assay was between 10−9 and 10−8 μg/ml. The chemotactic effect of TGF-β diminished when higher as well as lower concentrations (between 10−12 and 10−3 μg/ml) were employed. In contrast, inhibition of eosinophil survival induced by IL-3, IL-5 and GM-CSF reached its maximum at concentrations of TGF-β between 10−4 and 10−3 μg/ml. From these data we conclude that TGF-β in low concentrations can induce eosinophil chemotaxis whereas higher concentrations reduce eosinophil survival mediated by IL-3, IL-5 and GM-CSF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1998.00298.x
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  • 4
    Electronic Resource
    Electronic Resource
    Chemokine-receptor expression on T cells in lung compartments of challenged asthmatic patients (2005)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 35 (2005), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The interaction of chemokines with their receptors strongly influences the migration of leucocytes.Objective In order to assess the contribution of these molecules to the local recruitment of T cells in bronchial asthma, we analysed the expression of 14 chemokine receptors on lung-derived T cells.Methods Chemokine-receptor expression by T cells derived from the peripheral blood, the bronchoalveolar lavage fluid and the bronchial mucosa was analysed by flow cytometry and immunohistochemistry. Expression profiles in healthy and mildly asthmatic individuals were compared, the latter prior and after segmental allergen provocation.Results Compared with peripheral blood, alveolar T cells expressed significantly more CCR2, CCR5, CCR6, CXCR3 and CCR4. However, no differences were observed between healthy controls and unchallenged asthmatics. In patients developing significant inflammatory responses following specific allergen challenge, a marked increase in the percentage of CCR4+ and CCR7+, and reduced numbers of CXCR3-bearing alveolar T cells were detected. Following specific allergen challenge, chemokine-receptor expression profiles of T cells from the alveolar space and the mucosa or the submucosa were similar, excluding a particular subcompartmentalization of the chemokine/chemokine-receptor system.Conclusion The expression of certain chemokine receptors by lung T cells suggests a contribution to the physiological recruitment of T cells to the lungs, both in healthy controls and unchallenged mild asthmatics. However, strong allergen-induced airway responses were associated with a specific chemokine-receptor profile, suggesting the involvement of certain chemokine receptors in the pathogenesis of allergic bronchial inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.02132.x
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  • 5
    Electronic Resource
    Electronic Resource
    IgE antibodies to house dust, mite, animal allergens and moulds in house dust hypersensitivity (1976)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 6 (1976), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Fifty-three patients were investigated by intradermal tests and Phadebas RAST and, in most cases, the serum IgE level was determined. They were tested for sensitivity to house dust, Dermatophagoides pteronyssinus, cat, dog, horse and mould allergens.All cases with IgE antibodies to house dust were found to have specific IgE to other tested allergens as well. Eighty-nine per cent of the patients being RAST positive for house dust were also positive for D. pteronyssinus and in the majority of those cases IgE antibodies to other allergens were detected. The results reaffirm previous findings that the mite is not the only allergen in house dust and that extract of house dust is a mixture of several allergenic substances, which make it less suitable for differential testing.It is concluded that serum IgE determination is of value as a screening procedure in the diagnosis and that the use of a number of specific allergens in RAST is valuable in pinpointing the offending allergen in house dust hypersensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1976.tb01892.x
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  • 6
    Electronic Resource
    Electronic Resource
    Lack of increased numbers of low-density eosinophils in the circulation of asthmatic individuals (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 23 (1993), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The density distribution pattern of eosinophils over discontinuous isotonic Percoll gradients from the blood of normal, asymptomatic allergic and non-allergic asthmatic individuals was investigated. There was a completely identical distribution pattern between the investigated groups. Analysis of the expression of surface markers for complement receptors CR1 and CR3 and immunoglobulin G receptor on eosinophils derived from the density bands 1.080. 1.085 and 1.090 g/ml supported this finding since they did not reveal differences in expression between the bands within one group but also not between the three groups. Eosinophils of the various density bands were further purified and stimulated in vitro to produce leukotriene C4 (LTC4) by the calcium ionophore A23187 or serum treated zymosan. Equal amounts of LTC4 were synthesized by the eosinophils of the various density bands within one group. However, it appeared that the eosinophils of all density bands of allergic and non-allergic asthmatics synthesized significantly more LTC4 than the eosinophils from normal individuals (five-to tenfold). Probably this indicates in vivo priming of the eosinophils in asthmatic individuals which is not reflected by a change in density. Control experiments, dealing with possible artifacts due to the isolation procedure or the patient selection, to find differences in distribution patterns over discontinuous Percoll density gradients of the eosinophils of asthmatic compared to normal individuals failed to show such a difference. Therefore, the density distribution pattern of eosinophils over these gradients does not reflect cell activation, whereas LTC4 formation clearly does. This could mean that LTC4 formation is a more sensitive parameter for cell activation than density distribution or cell surface marker expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1993.tb00320.x
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  • 7
    Electronic Resource
    Electronic Resource
    Altered distribution of IgG subclasses in aspirin-induced asthma: high IgG4, low IgG1 (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 22 (1992), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have determined IgG subclass concentrations in 100 patients with aspirin-induced asthma and 80 healthy controls. Patients on chronic corticotherapy (n= 64) had significantly lower total IgG levels than patients not receiving steroids (n= 36) or controls. Corticotherapy was not associated with changes in the subclass distributions. In patients, the most striking finding was elevation of IgG4. It was not related to corticotherapy or serum IgE levels. The rise in IgG4 was accompanied by a modest, though statistically significant, depression of IgG1. No changes of IgG2 and IgG3 concentrations were observed. Thus, aspirin-induced asthma is characterized by a distinct pattern of distributions of IgG subclasses. It is suggested that in aspirin-induced asthma elevation of IgG4 might result from chronic antigenic stimulation, of viral origin, and that determination of IgG subclass distribution might be of clinical interest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1992.tb03084.x
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  • 8
    Electronic Resource
    Electronic Resource
    Delayed generation of thrombin in clotting blood of atopic patients with hayfever and asthma (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There have been several reports on alterations of platelet function and raised plasma heparin levels in symptom-free atopic subjects. Either of these can affect formation of thrombin in vivo. In 25 symptom-free atopic patients and 32 healthy volunteers we studied the generation of thrombin in blood emerging from a standardized skin microvasculature injury, which also served to determine bleeding time. Generation of thrombin was delayed in atopies. They produced significantly less thrombin (P〈0.01) during the early and central phase of haemostasis. The amount of thrombin generated was inversely correlated to bleeding time, which in atopies was on average 50 sec longer than in controls (P= 0.055). Two hours after ingestion of 500 mg aspirin, this difference increased up to 150 sec, although the individual responses varied markedly (P= 0.08), while the generation of thrombin became strongly depressed in both groups. The possible clinical relevance of the delayed formation of thrombin in atopy awaits further studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1991.tb01680.x
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  • 9
    Electronic Resource
    Electronic Resource
    Increase in killer-specific secretory protein of 37 kDa in bronchoalveolar lavage fluid of allergen-challenged patients with atopic asthma (2005)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 35 (2005), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Atopic asthma is linked to a T-helper type 2 dominated pathogenesis, but there is increasing evidence of Th1/Tc1-mediated processes in the aetiopathology of asthma. Killer-specific secretory protein of 37 kDa (Ksp37) is expressed in cytotoxic lymphocytes, selectively in the effector subsets of CD8+- and CD4+ T lymphocytes and in CD16+/CD56dim natural killer cells and γ/δ T cells. This effector cell-specific expression of Ksp37 and its coexpression with perforin suggest that Ksp37 might be involved in processes mediated by cytotoxic cells.Objective We hypothesize that Ksp37 could indicate the involvement of cytotoxic lymphocytes in the pathogenesis of atopic asthma, and investigated Ksp37 concentration in bronchoalveolar lavage fluid (BALF) collected 10 min, 18, 42 or 162 h after segmental allergen provocation and in serum of patients with atopic asthma (n=25).Methods Ksp37 concentrations in BALF and serum were detected by ELISA. Flow cytometric analysis was used to assess numbers and cell subsets in BALF.Results Ksp37 increased significantly in BALF 10 min, 18 and 42 h, but not 162 h after allergen challenge compared with saline-challenged controls, while Ksp37 serum levels did not change significantly at all time-points. In addition, the increase in Ksp37 concentrations in BALF correlated with the corresponding numbers of lymphocytes.Conclusions We conclude that Ksp37 level increased in BALF 10 min, 18 and 42 h after allergen challenge but not in peripheral blood. Our findings suggest that segmental allergen challenge in asthma is associated with an increase in Ksp37 concentrations in BALF and an influx of potentially cytotoxic T lymphocytes into the lungs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2005.02238.x
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  • 10
    Electronic Resource
    Electronic Resource
    Interleukin-5 receptors on human lung eosinophils after segmental allergen challenge (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background IL-5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge.Objective The action of IL-5 is mediated via the specific IL-5 receptor-α (IL-5Rα). Although in vitro data suggest that IL-5R expression is regulated by cytokines such as IL-3, IL-5 and GM-CSF, IL-5R regulation in vivo and its kinetics following allergen provocation are incompletely understood.Methods We investigated IL-5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL-5Rα was measured by flow cytometry and IL-5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA.Results IL-5Rα expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL-5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL-5 concentrations in serum 18 or 42 h after allergen exposure.Conclusions Although there was no correlation between IL-5 concentrations and IL-5Rα expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL-5 concentrations and IL-5Rα expression on eosinophils.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.01986.x
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