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The mechanisms of serum-treated zymosan (STZ)-induced oxidative metabolism by human eosinophils and the effects of IL-5 priming
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2001 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 56, no 7, 639-645 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The aim of this work was to study the mechanisms of action of IL-5 on the subsequent stimulation of the oxidative metabolism of blood eosinophils by serum-treated zymosan (STZ), in terms of signal transduction characteristics, and by comparing the response of cells from healthy and allergic subjects during environmental exposure to birch pollen.

METHODS: Eosinophils from healthy controls and allergic patients were purified to over 95% by Percoll gradients and the MACS system. Oxidative metabolism was measured by a lucigenin-enhanced chemiluminescence (CL) assay. Eosinophils were primed with IL-5 and subsequently stimulated with STZ. The signal transduction mechanisms of IL-5 priming were studied with the MEK inhibitor PD 98059,the PkC inhibitors staurosporine and Ro 318220, and the PI3 kinase inhibitor wortmannin.

RESULTS: IL-5 increased the maximum radical production (P=0.0079) and reduced the t(1/2) rise (0.000018) of the CL reactions. The t(1/2) rise was PkC dependent and MEK independent, while the maximum radical production was PkC, MEK, and PI3 kinase dependent. During the pollen season, IL-5 reduced the total STZ-induced CL response in the patients' cells (P=0.016), but not in the control cells, whereas it primed the response to STZ of both cell populations in terms of the t(1/2) rise (P=0.012 and 0.00066, respectively).

CONCLUSION: STZ-induced oxidative metabolism consists of different stages. The initial stage (t(1/2) rises of the curves) is PkC dependent and MEK independent, while the end stage (maximum radical production) is PkC, MEK, and PI3 kinase dependent. IL-5 shortened the initial stage, and increased the end stage. During allergen exposure, however, the end stage was reduced by IL-5. This could be due to increased amounts of hypodense eosinophils and/or some abnormality in cell responses.

Place, publisher, year, edition, pages
2001. Vol. 56, no 7, 639-645 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-54800DOI: 10.1034/j.1398-9995.2001.00898.xPubMedID: 11421922OAI: oai:DiVA.org:uu-54800DiVA: diva2:82709
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2010-11-24Bibliographically approved

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