Document Detail

Prevention of F-actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells.
MedLine Citation:
PMID:  23616175     Owner:  NLM     Status:  MEDLINE    
Following antigen/IgE-mediated aggregation of high affinity IgE-receptors (FcεRI), mast cells (MCs) degranulate and release inflammatory mediators leading to the induction of allergic reactions including anaphylaxis. Migration of MCs to resident tissues and sites of inflammation is regulated by tissue chemotactic factors such as stem cell factor (SCF (KIT ligand)). Despite inducing similar early signaling events to antigen, chemotactic factors, including SCF, produce minimal degranulation in the absence of other stimuli. We therefore investigated whether processes regulating MC chemotaxis are rate limiting for MC mediator release. To investigate this issue, we disrupted actin polymerization, a requirement for MC chemotaxis, with latrunculin B and cytochalasin B, then examined chemotaxis and mediator release in human (hu)MCs induced by antigen or SCF. As expected, such disruption minimally affected early signaling pathways, but attenuated SCF-induced human mast cell chemotaxis. In contrast, SCF, in the absence of other stimuli, induced substantial degranulation in a concentration-dependent manner following actin disassembly. It also moderately enhanced antigen-mediated human mast cell degranulation which was further enhanced in the presence of SCF. These observations suggest that processes regulating cell migration limit MC degranulation as a consequence of cytoskeletal reorganization.
Daniel Smrž; Geethani Bandara; Michael A Beaven; Dean D Metcalfe; Alasdair M Gilfillan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2013-06-04
Journal Detail:
Title:  European journal of immunology     Volume:  43     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-05     Completed Date:  2013-09-09     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1873-82     Citation Subset:  IM    
Copyright Information:
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Actins / immunology,  metabolism*
Cell Degranulation / drug effects,  immunology*
Cells, Cultured
Chemotaxis, Leukocyte / drug effects,  immunology*
Flow Cytometry
Mast Cells / immunology,  metabolism*
Microscopy, Confocal
Stem Cell Factor / immunology*,  pharmacology
Grant Support
Reg. No./Substance:
0/Actins; 0/Stem Cell Factor
Comment In:
Eur J Immunol. 2013 Jul;43(7):1698-701   [PMID:  23719840 ]

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