| Heterogeneity in the responses of human lung mast cells to stem cell factor. | |
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MedLine Citation:
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PMID: 23278880 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: Stem cell factor (SCF) is a growth factor that is involved in mast cell differentiation and proliferation. SCF primes human lung mast cells for enhanced responses to IgE-directed activation but is not generally recognized as a direct activator. SCF mediates its effects through c-kit. OBJECTIVE: The aim of this study was to reappraise the effects of SCF on human lung mast cells. METHODS: Mast cells were isolated from human lung. Mast cells were challenged with anti-IgE or SCF and the generation of histamine, cysteinyl-leukotrienes (cys-LTs) and prostaglandin D(2) (PGD(2) ) was assessed as was expression of the activation marker, CD63. The effects of c-kit inhibitors on mediator release were evaluated. RESULTS: Stem cell factor (10 ng/mL) alone was unable to induce mediator release but primed mast cells for enhanced IgE-dependent secretion. At higher concentrations (≥ 30 ng/mL), SCF had more varied effects and even when used alone was able to drive substantial levels of histamine release in about a third of all preparations studied. Similarly, SCF (100 ng/mL) alone was effective in stimulating the generation of cys-LTs in half of the preparations studied. SCF (100 ng/mL) was even more effective at stimulating PGD(2) generation as almost all preparations generated substantial quantities of the prostanoid. Mediator release induced by SCF was accompanied by the up-regulation of the activation marker, CD63. There was a positive correlation between the extent of mediator release induced by SCF and c-kit receptor expression. The effects of SCF on mediator release from mast cells were reversed by the c-kit inhibitor imatinib. CONCLUSIONS AND CLINICAL RELEVANCE: These data demonstrate that the responses of mast cells to SCF are heterogeneous. SCF can drive much greater levels of mediator release from mast cells, especially of PGD(2) , than hitherto appreciated and this could be important in the context of respiratory diseases. |
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Authors:
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A Lewis; J Wan; B Baothman; P N Monk; S K Suvarna; P T Peachell |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology Volume: 43 ISSN: 1365-2222 ISO Abbreviation: Clin. Exp. Allergy Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8906443 Medline TA: Clin Exp Allergy Country: England |
Other Details:
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Languages: eng Pagination: 50-9 Citation Subset: IM |
Copyright Information:
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© 2012 Blackwell Publishing Ltd. |
Affiliation:
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Academic Unit of Respiratory Medicine, The Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. |
Export Citation:
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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