Document Detail


Complex chemoattractive and chemorepellent Kit signals revealed by direct imaging of murine mast cells in microfluidic gradient chambers.
MedLine Citation:
PMID:  23835699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Besides its cooperating effects on stem cell proliferation and survival, Kit ligand (KL) is a potent chemotactic protein. While transwell assays permit studies of the frequency of migrating cells, the lack of direct visualization precludes dynamic chemotaxis studies. In response, we utilize microfluidic chambers that enable direct observation of murine bone marrow-derived mast cells (BMMC) within stable KL gradients. Using this system, individual Kit+ BMMC were quantitatively analyzed for migration speed and directionality during KL-induced chemotaxis. Our results indicated a minimum activating threshold of ~3 ng ml(-1) for chemoattraction. Analysis of cells at KL concentrations below 3 ng ml(-1) revealed a paradoxical chemorepulsion, which has not been described previously. Unlike chemoattraction, which occurred continuously after an initial time lag, chemorepulsion occurred only during the first 90 minutes of observation. Both chemoattraction and chemorepulsion required the action of G-protein coupled receptors (GPCR), as treatment with pertussis toxin abrogated directed migration. These results differ from previous studies of GPCR-mediated chemotaxis, where chemorepulsion occurred at high ligand concentrations. These data indicate that Kit-mediated chemotaxis is more complex than previously understood, with the involvement of GPCRs in addition to the Kit receptor tyrosine kinase and the presence of both chemoattractive and chemorepellent phases.
Authors:
Amir Shamloo; Milan Manchandia; Meghaan Ferreira; Maheswaran Mani; Christopher Nguyen; Thomas Jahn; Kenneth Weinberg; Sarah Heilshorn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Integrative biology : quantitative biosciences from nano to macro     Volume:  5     ISSN:  1757-9708     ISO Abbreviation:  Integr Biol (Camb)     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-07-23     Completed Date:  2014-02-10     Revised Date:  2014-04-09    
Medline Journal Info:
Nlm Unique ID:  101478378     Medline TA:  Integr Biol (Camb)     Country:  England    
Other Details:
Languages:  eng     Pagination:  1076-85     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / cytology*
Cell Culture Techniques
Cells, Cultured
Chemotaxis / drug effects,  physiology*
GTP-Binding Proteins / chemistry
Image Processing, Computer-Assisted
Mast Cells / cytology*,  drug effects
Mice
Mice, Inbred C57BL
Microfluidic Analytical Techniques*
Microfluidics / methods
Pertussis Toxin / chemistry
Receptors, G-Protein-Coupled / metabolism*
Signal Transduction
Stem Cell Factor / chemistry*
Grant Support
ID/Acronym/Agency:
CA049605/CA/NCI NIH HHS; DP2 OD006477/OD/NIH HHS; DP2-OD006477-01/OD/NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, G-Protein-Coupled; 0/Stem Cell Factor; EC 2.4.2.31/Pertussis Toxin; EC 3.6.1.-/GTP-Binding Proteins
Comments/Corrections

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


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