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B Wedi

Publications and source records attributed to B Wedi.

28 records · Page 2Linked to original sources
PubMed1998

IL-4-induced apoptosis in peripheral blood eosinophils.

BACKGROUND: The regulation of eosinophil survival and apoptosis may play a major role in diseases demonstrating increased numbers of circulating and tissue eosinophils such as allergic reactions. Because few promoters of eosinophil apoptosis have been described so far, the objective of this study was to elucidate the role of endogenous factors on eosinophil survival and apoptosis. METHODS AND RESULTS: Highly purified peripheral blood eosinophils were analyzed in the time course from 24 up to 144 hours in culture. Eosinophil survival was assessed with trypan blue dye exclusion and apoptosis was determined by DNA fragmentation gel analysis and ELISA technique with anti-histone antibodies. We confirmed previous results demonstrating prolonged eosinophil survival and inhibited apoptosis by IL-3, IL-5, and GM-CSF. In contrast, eosinophil apoptosis was significantly enhanced by corticosteroids, particularly dexamethasone and hydrocortisone. However, IL-1beta, IL-8, IL-12, platelet-activating factor, TNF-alpha, and eotaxin had no effect on eosinophil survival or apoptosis when compared with culture medium alone. In contrast, IL-4 at concentrations of 100 U/mL or more inhibited eosinophil survival and induced apoptosis. This effect was time dependent and abrogated by preincubation with neutralizing anti-IL-4 antibodies. However, after 96 hours in coincubation, IL-4 did overcome the survival-prolonging effect of IL-3, IL-5, and GM-CSF. IL-4 did not enhance eosinophil surface expression of APO-1/Fas antigen (CD95). In assessing IL-4-mediated effects on eosinophil function, we found no response by means of the release of eosinophil cationic protein or reactive oxygen species. CONCLUSIONS: Taken together, our data present direct evidence for the presence of functional IL-4 receptors on human eosinophils and indicate that IL-4 may lead to resolution of chronic inflammation by induction of eosinophil apoptosis.

Apoptosis↗
PubMed1998

Prevalence of Helicobacter pylori-associated gastritis in chronic urticaria.

BACKGROUND: Chronic urticaria and concurrent angioedema are frustrating problems for both physicians and patients. METHODS: 100 patients with chronic urticaria (mean duration 33.3+/-48.2 months) attending the urticaria consulting hour of our Department of Dermatology within 1 year were carefully analyzed for pathogenesis to avoid extensive unnecessary diagnostic approach in the future. RESULTS: In 43 cases a potential infectious trigger could be identified, 35 were of idiopathic origin, and 15 demonstrated pseudoallergic reactions to acetylsalicylic acid or food additives, 5 had antibodies to thyroid gland, and 2 had malignant diseases. Of patients with foci, 26 had Helicobacter pylori-associated gastritis, 9 chronic tonsillitis or sinusitis, 4 infections with Epstein-Barr virus or cytomegalovirus, 2 dental focal infections and 2 suffered from Yersinia infection. High prevalence of H. pylori gastritis was found since 47% of patients showed elevated H. pylori-specific IgA and/or IgG antibodies. 27 patients underwent endoscopy and in all but 1 (96%) antral H. pylori infection was found. In contrast, a prevalence rate of 37% among asymptomatic adults has been published. Disappearance (67%) or improvement of urticaria (24%) occurred in most antimicrobially treated patients after 3-12 weeks. In contrast, only 50% of untreated H. pylori-seropositive patients with chronic urticaria showed spontaneous remission or improvement within 12 weeks. Prevalence of H. pylori infection may even be underestimated since only 27/100 patients underwent endoscopy. It is suggested that H. pylori infection may be present at least in all seropositive subjects (47%). Moreover, we found H. pylori infection in 2 seronegative subjects demonstrating gastric complaints. CONCLUSIONS: Thus, measurement of H. pylori-specific antibodies and/or gastroscopy should be included in the diagnostic management of chronic urticaria to identify patients who may profit from eradication treatment with disappearance of long-standing and annoying urticaria symptomatology.

Adolescent↗
PubMed1997

Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis.

The present studies were undertaken to characterize the potential role of eosinophil programmed cell death (PCD) in atopic diseases. Peripheral blood eosinophil PCD was found to be delayed in inhalant allergy (p < 0.05) and delayed to an even greater extent in atopic dermatitis (AD) (p < 0.0001) when compared to nonatopic subjects. There was no difference in the occurrence of PCD between the extrinsic and the intrinsic type of AD, pointing to a secondary role of specific sensitization. Blockade of eosinophil PCD was not responsible for peripheral blood eosinophilia, because we found no obvious relationship of eosinophil survival to blood eosinophil count. Eosinophil supernatants of more patients with AD than of patients with inhalant allergy dose-dependently inhibited PCD in nonatopic eosinophils, and it was shown that this effect was possibly due to autocrine production of granulocyte-macrophage-colony stimulating factor, probably IL-5. Eosinophil expression of CD95 (Fas antigen) did not change over time in culture and was not modulated by cytokines prolonging eosinophil survival. In contrast, IL-3, IL-5, and granulocyte-macrophage-colony stimulating factor caused an upregulated expression of CD69. However, in AD, CD69 on eosinophils was upregulated without the need of exogenous growth factor or factors over time in culture, thus confirming an autocrine production of proeosinophilic cytokines. In conclusion, our data clearly indicate that eosinophil PCD is markedly delayed in the so-called atopic diseases irrespective of allergen sensitization and suggest that this effect is mediated by the autocrine production of growth factors by eosinophils.

Adult↗
PubMed1997

Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergy.

BACKGROUND: The clinical relevance of gastrointestinal food allergy in adults is largely unknown because the mechanisms are poorly understood and the diagnosis is difficult to confirm. AIMS: To improve the diagnostic means for confirming intestinal food allergy on an objective basis, a new colonoscopic allergen provocation (COLAP) test was developed. PATIENTS: The COLAP test was performed in 70 adult patients with abdominal symptoms suspected to be related to food allergy, and in five healthy volunteers. METHODS: During the COLAP test, the caecal mucosa was challenged endoscopically with three food antigen extracts, a buffer control, and a positive control (histamine). The mucosal weal and flare reaction was registered semiquantitatively 20 minutes after challenge, and tissue biopsy specimens were examined for mast cell and eosinophil activation. RESULTS: No severe systemic anaphylactic reactions were found in response to intestinal challenge. The COLAP test was positive to at least one food antigen in 54 of 70 patients (77%), whereas no reaction in response to antigen was found in healthy volunteers. Antigen induced weal and flare reactions were correlated with intestinal mast cell and eosinophil activation, as well as with patients' history of adverse reactions to food, but not with serum concentrations of total or specific IgE or skin test results. CONCLUSION: The COLAP test may be a useful diagnostic measure in patients with suspected intestinal food allergy and may provide a new tool for the study of underlying mechanisms.

Adolescent↗
PubMed1996

Human HMC-1 mast cells exclusively express the Fc gamma RII subtype of IgG receptor.

Because of their localization at the interface of the internal and external environment mast cells play a crucial role in the immune response and in inflammatory reactions. Effects may be mediated not only by the high-affinity IgE receptor, but also by IgG receptors. Since in rodent mast cells signal transduction via the Fc gamma receptor family has been shown, we analysed the expression of surface receptors for IgG on the human mast cell line HMC-1. It was shown by flow cytometric analysis that HMC-1 constitutively expressed the Fc gamma RII/CD32 subtype whereas Fc gamma RI/CD64 and Fc gamma RIII/CD16 were not expressed. This exclusive expression of the Fc gamma RII subtype of IgG receptor is similar to the expression pattern of basophils, although concerning cell surface molecules HMC-1 rather seem to resemble monocytes. In contrast to monocytes the expression profile on HMC-1 did not change upon stimulation with IL-4, TNF alpha, IFN gamma, PMA or salbutamol. Moreover, the mast cell-activating cytokine SCF and the calcium ionophore A23187 did not modulate the Fc gamma R profile in this study. To assess the importance of the exclusive Fc gamma RIII expression on HMC-1, we investigated whether the production of the cytokine TNF alpha is modulated via Fc gamma RII activation or if an increase in intracellular calcium could be observed. No significant modulation of TNF alpha release or of intracellular free calcium after crosslinking of Fc gamma RII by heat-aggregated IgG or by a second antibody was observed. It remains to be clarified whether this low-affinity subtype for the IgG receptor is involved in antigen-dependent sensitization of human tissue mast cells resulting in secretion of immunoregulatory cytokines. This mechanism may be important for disease states associated with circulating or tissue-bound immune complexes.

Albuterol↗
PubMed1996

Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on the human mast-cell line (HMC)-1 by inflammatory mediators.

The effect of inflammatory mediators on the expression of several surface adhesion molecules on the human mast-cell line (HMC)-1 was studied. By flow cytometry, it could be shown that among several surface adhesion molecules (ICAM-1/CD54, VLA-4/CD49d, Mac-1/CD11b, LFA-1/CD11a, LFA-2/CD2, LFA-3/CD58, VCAM-1), only the constitutively expressed immunoglobulin family member intercellular adhesion molecule-1 (ICAM-1) is modulated by proinflammatory cytokines on HMC-1 mast cells. Stimulation with tumor necrosis factor-a (TNF-alpha) and interferon-gamma (IFN-gamma) resulted, in addition to interleukin-(IL-)4, in selective upregulation of ICAM-1 expression. Costimulation of either IL-4 or IFN-gamma with TNF-alpha further increased the ICAM-1 expression as compared to the stimuli alone. In contrast, stem-cell factor (SCF), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-10, IL-8, monocyte chemotactic and activating factor (MCAF), and the complement split product C5a failed to modulate the expression of any adhesion molecule examined. The levels of cytoplasmic free calcium in HMC-1 mast cells were not altered by cross-linking surface ICAM-1, suggesting linkage of other intracellular signaling pathways. This cytokine-induced upregulation of ICAM-1 expression might reveal a putative regulatory mechanism of mast-cell interaction with effector cells bearing the counterparts of ICAM-1 (CD54), the molecules Mac-1 (CD11b/CD18) and leukosialin (CD43), and the principal ligand LFA-1 (CD11a/CD18).

Cytokines↗
PubMedDate not supplied

Chronic urticaria: clinical aspects and focus on a new antihistamine, levocetirizine.

Chronic urticaria (CU) involves release of histamine from mast cells and/or basophils, which in turn promotes the classic inflammatory cascade. The resultant symptoms can severely impact sufferers' quality of life and in severe cases prevent them from leading a normal existence, with consequent burdens on family and society. Rapid initiation of effective reliable therapy is important in combating CU, together with avoidance of triggers or exacerbating factors, if known. While newer immunologically-based therapies are beginning to be developed, antihistamines remain a cornerstone of effective therapy. Treatment should be tailored to individual patient circumstances, but in principle the choice of antihistamine component should be governed by the availability of evidence of rapid and prolonged efficacy specifically in CU and evidence of good tolerability and safety. Increasingly, evidence of beneficial effects on patient quality of life is also required for rational selection of an antihistamine from amongst those available. Levocetirizine is a new single-isomer antihistamine with a proven efficacy on chronic urticaria as documented in two recent clinical studies, which have included effectiveness and quality of life assessments.

Cetirizine↗