Biomedical subjects

Kurt Blaser

Publications and source records attributed to Kurt Blaser.

58 records · Page 4Linked to original sources

PubMed2002

Immune regulation by histamine.

Histamine is a potent bioamine with multiple activities in various pathological and physiological conditions. In addition to its well-characterised effects in the acute inflammatory and allergic responses, histamine regulates several aspects of antigen-specific immune response development. Histamine affects the maturation of dendritic cells and alters their T cell-polarising capacity. Histamine also regulates antigen-specific T helper 1 and T helper 2 cells, as well as related antibody isotype responses. Apparently, diverse effects of histamine on immune regulation are because of differential expression of four types of histamine receptors and their distinct intracellular signals.

Animals↗

PubMed2002

T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma.

BACKGROUND: Asthma is an inflammatory airway disease associated with an infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (ECs). OBJECTIVE: Shedding of bronchial ECs is characterized by loss of the normal bronchial pseudostratified epithelium and the maintenance of a few basal cells on a thickened basement membrane. The aim of this study was to investigate whether, and by which mechanism, T cells and eosinophils can cause damage to airway ECs. METHODS: Bronchial ECs, cultured and exposed to cytokines, eosinophil cationic protein, activated T cells, and eosinophils were studied for the expression of apoptosis receptors (flow cytometry, immunoblotting, and RNA expression) and for the susceptibility for undergoing apoptosis. In addition, bronchial biopsy specimens from patients with asthma were evaluated for EC apoptosis. RESULTS: We demonstrate herein that the respiratory epithelium is an essential target of the inflammatory attack by T cells and eosinophils. Bronchial ECs underwent cytokine-induced cell death with DNA fragmentation and morphologic characteristics of apoptosis mediated by activated T cells and eosinophils. T cell- and eosinophil-induced EC apoptosis was blocked by inhibition of IFN-alpha and TNF-alpha; the Fas ligand-Fas pathway appears to be less important. Recombinant eosinophil cationic protein induced mainly necrosis of ECs. Furthermore, we demonstrated in situ apoptotic features of ECs in bronchial biopsy specimens of asthmatic patients. CONCLUSION: T cell- and eosinophil-induced apoptosis represents a key pathogenic event leading to EC shedding in asthma.

Apoptosis↗

PubMed2002

Immunological and structural analysis of IgE-mediated cross-reactivity between manganese superoxide dismutases.

BACKGROUND: Allergy results from inappropriate immune responses to normally innocuous proteins. More than 300 IgE-binding proteins have been cloned and shown to cover structurally and functionally heterogeneous protein families including enzymes, backbone and storage proteins as well as proteins with unknown function. Structurally related cross-reactive allergens are involved in the pathogenesis of important clinical syndromes. We found that phylogenetically highly conserved proteins, including human manganese superoxide dismutase (MnSOD), are involved in IgE-mediated autoreactivity. METHODS: MnSOD cloned from different phylogenetically distant species were produced as recombinant proteins in Escherichia coli and used to study IgE-mediated cross-reactivity and proliferative responses in peripheral blood mononuclear cells (PBMC) of individuals sensitised to Aspergillus fumigatus MnSOD. Homology models of the three-dimensional structures of MnSOD from A. fumigatus, Drosophila melanogaster and Saccharomyces cerevisiae using the human MnSOD structure refined at 2.2 A as template were constructed to identify conserved amino acid residues exposed to the solvent. RESULTS: Cross-reactivity between the MnSOD at B and T cell level was demonstrated by inhibition experiments showing shared B cell epitopes and by the capability of the different MnSODs to induce proliferative responses in PBMCs of sensitised individuals. Structural modelling allowed to identify conserved residues exposed to the solvent. The identified residues are scattered over the sequence of the enzyme indicating putative conformational IgE-binding epitopes. CONCLUSIONS: The results obtained corroborate molecular mimicry as a plausible mechanism to explain autoreactivity to human MnSOD. Moreover, homology modelling provides a rational tool to identify conserved residues involved in defining cross-reactive B cell epitopes.

Adult↗

PubMedDate not supplied

T regulatory cells in allergen-specific immunotherapy.

A dramatic increase in the prevalence of allergy and asthma has occurred during the past few decades. Although the symptoms of many allergic disorders can be suppressed quite effectively by pharmacological interventions, these do not provide a curative solution and therefore involve lifelong use of medication. Allergen-specific immunotherapy (SIT) on the other hand provides a long-lasting effect on the immune response to common environmental antigens, therefore allowing cessation of the therapy after several years. The changes in the immune response brought about by allergen-SIT are slowly being unveiled and explained. Mechanisms underlying allergen-SIT and in particular the role of regulatory T cells will be discussed in this review, based on recent findings and current concepts.

Allergens↗