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Heterogeneity in the responses of human lung mast cells to stem cell factor.
MedLine Citation:
PMID:  23278880     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
A Lewis; J Wan; B Baothman; P N Monk; S K Suvarna; P T Peachell
Publication Detail:
Type:  Journal Article    
Journal Detail:
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:
Created Date:  2013-01-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8906443     Medline TA:  Clin Exp Allergy     Country:  England    
Other Details:
Languages:  eng     Pagination:  50-9     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Academic Unit of Respiratory Medicine, The Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK.
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