Document Detail

Interaction between activated chemokine receptor 1 and FcepsilonRI at membrane rafts promotes communication and F-actin-rich cytoneme extensions between mast cells.
MedLine Citation:
PMID:  20173038     Owner:  NLM     Status:  MEDLINE    
Chemokines play important regulatory roles in immunity, but their contributions to mast cell function remain poorly understood. We examined the effects of FcepsilonRI-chemokine receptor (CCR) 1 co-stimulation on receptor localization and cellular morphology of bone marrow-derived mast cells. Whereas FcepsilonRI and CCR1 co-localized at the plasma membrane in unsensitized cells, sensitization with IgE promoted internalization of CCR1 molecules. Co-stimulation of FcepsilonRI and CCR1 with antigen and macrophage inflammatory protein-1alpha was more effective than FcepsilonRI stimulation alone in causing leading edge formation, flattened morphology, membrane ruffles and ganglioside (GM1(+)) lipid mediator release. Co-stimulation resulted in phalloidin-positive cytoneme-like cellular extensions, also known as tunneling nanotubes, which originated at points of calcium accumulation. This is the first report of cytoneme formation by mast cells. To determine the importance of lipid rafts for mast cell function, the cells were cholesterol depleted. Cholesterol depletion enhanced degranulation in resting, sensitized and co-stimulated cells, but not in FcepsilonRI-cross-linked cells, and inhibited formation of filamentous actin(+) cytonemes but not GM1(+) cytonemes. Treatment with latrunculin A to sequester globular-actin abolished cytoneme formation. The cytonemes may participate in intercellular communication during allergic and inflammatory responses, and their presence in the co-stimulated mast cells suggests new roles for CCRs in immunopathology.
Nimita H Fifadara; Freddy Beer; Shoichiro Ono; Santa J Ono
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International immunology     Volume:  22     ISSN:  1460-2377     ISO Abbreviation:  Int. Immunol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-22     Completed Date:  2010-05-20     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  8916182     Medline TA:  Int Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  113-28     Citation Subset:  IM    
Dobbs Ocular Immunology Laboratories, Department of Ophthalmology, Emory Eye Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
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MeSH Terms
Actins / metabolism*
Bicyclo Compounds, Heterocyclic / pharmacology
Calcium Signaling
Cell Communication* / drug effects
Cell Shape
Cells, Cultured
Chemokine CCL3 / metabolism
Cholesterol / deficiency
G(M1) Ganglioside / metabolism
Mast Cells / drug effects,  immunology,  metabolism*
Membrane Microdomains / drug effects,  immunology,  metabolism*
Mice, Inbred BALB C
Protein Transport
Receptors, CCR1 / genetics,  metabolism*
Receptors, IgE / metabolism*
Recombinant Proteins / metabolism
Thiazolidines / pharmacology
Time Factors
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Actins; 0/Bicyclo Compounds, Heterocyclic; 0/CCL3 protein, human; 0/Ccr1 protein, mouse; 0/Chemokine CCL3; 0/Receptors, CCR1; 0/Receptors, IgE; 0/Recombinant Proteins; 0/Thiazolidines; 37758-47-7/G(M1) Ganglioside; 57-88-5/Cholesterol; 76343-93-6/latrunculin A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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