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Cytokine-regulated eosinophil migration in inflammatory disorders: Clinical and experimental studies
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The accumulation of eosinophil granulocytes (EOS) at sites of inflammation is a common feature of astma, allergic rhinitis and inflammatory bowel disease. The aim of the present investigation was to study the mechanisms involved in this accumulation.

Bronchoalveolar lavage (BAL) fluid obtained from patients with birch-pollen allergy lavaged during season exhibited increased eosinophil chemotactic activity compared with pre-season BAL fluid from the same patients. We identified IL-5, IL-8 and RANTES as the main eosinophil chemotactic agents in the BAL fluid. Only EOS from allergic donors responded to IL-8. IL-2 inhibited albumin-stimulated eosinophil migration towards buffer or chemoattractants. EOS from allergic subjects were less sensitive to this inhibition than EOS from normal subjects, and in vitro priming of the EOS with IL-5 prevented the inhibitory effect of IL-2. We therefore hypothesise that IL-2 acts as an autocrine regulator of EOS migration, and that this inhibitory effect may be down-regulated in allergy, resulting in increased migration of EOS towards chemotactic factors. The stimulation of eosinophil migration by albumin is mediated by PI3 kinase. Decreased expression of CD49d and CD49f caused by albumin may decrease the adhesiveness of the EOS, which in turn may facilitate migration. We found a higher chemotactic activity in perfusion fluids from patients with ulcerative colitis than from control patients. The chemotactic activity correlated with the concentrations of eosinophil granule proteins in the perfusion fluids. IL-5 and TNF-α were identified as two of the chemotactic agents in the perfusion fluid that were inhibited by steroid treatment. Agents with steroid-insensitive chemotactic activity remain to be identified.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2000. , p. 58
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 971
Keywords [en]
Medical sciences, Eosinophil, cytokine, migration, inflammation, asthma, allergy, inflammatory bowel disease, ulcerative colitis
Keywords [sv]
MEDICIN OCH VÅRD
National Category
Medical and Health Sciences
Research subject
Clinical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-528ISBN: 91-554-4849-6 (print)OAI: oai:DiVA.org:uu-528DiVA, id: diva2:166019
Public defence
2000-12-06, Stora Aulan, akademiska sjukhuset, ing.50, bottenvåningen., Uppsala, 09:15
Available from: 2000-11-15 Created: 2000-11-15Bibliographically approved

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Citation style
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