Inhibitory effects of ketotifen on eotaxin-dependent activation of eosinophils: consequences for allergic eye diseases
| Autor: | C. Schoch, Sylvie Loiseau, M. Loyens, Monique Capron, Gaetane Woerly |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Chemokine CCL11
Ketotifen Eotaxin Eye Diseases Cell Survival Chemotactic Factors Eosinophil Immunology Eosinophil-derived neurotoxin Eosinophil-Derived Neurotoxin Ribonucleases Anti-Allergic Agents medicine Humans Immunology and Allergy Interleukin 5 Eosinophil cationic protein Dose-Response Relationship Drug Chemistry Degranulation Chemotaxis Blood Proteins respiratory system Eosinophil Eosinophils N-Formylmethionine Leucyl-Phenylalanine Chemotaxis Leukocyte medicine.anatomical_structure Case-Control Studies Chemokines CC Interleukin-5 Reactive Oxygen Species Oxidation-Reduction medicine.drug |
| Zdroj: | Allergy. 58:397-406 |
| ISSN: | 1398-9995 0105-4538 |
| DOI: | 10.1034/j.1398-9995.2003.00081.x |
| Popis: | Background: The aim of this study was to investigate the effects of ketotifen on different parameters of human eosinophil functions, namely chemotaxis, oxidative metabolism and mediator release, induced after activation. Methods: Eosinophils from hypereosinophilic patients or normal donors were purified by Percoll gradient and the magnetic cell separation system. Chemotaxis was studied using the Boyden chamber technique using three potent chemoattractants: formyl-methionine-leucine-phenylalanine (fMLP), interleukin (IL)-5 and eotaxin. Oxidative metabolism was determined by a luminol-dependent chemiluminescence assay after activation with eotaxin or secretory immunoglobulin A (sIgA). The release of eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN) was measured by radioimmunoassay after activation with sIgA. Results: At pharmacologically active concentrations and in a dose-dependent manner, ketotifen significantly inhibited the chemotaxis of eosinophils to fMLP, IL-5 and eotaxin. The production of reactive oxygen species induced by eotaxin and sIgA was decreased by ketotifen, showing a more pronounced effect when cells were activated by eotaxin. Activation by sIgA resulted in ECP and EDN release, which was partially inhibited by ketotifen. Conclusions: Through inhibition of chemotaxis, ketotifen might limit the number of eosinophils at the inflammation site during allergic reaction. Furthermore, inhibition by ketotifen of main inflammatory mediators release suggests a potential role of the drug in limiting the pathological potential of eosinophils. |
| Databáze: | OpenAIRE |
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