Document Detail

Toll-like receptor-mediated eosinophil-basophil differentiation: autocrine signalling by granulocyte-macrophage colony-stimulating factor in cord blood haematopoietic progenitors.
MedLine Citation:
PMID:  23347362     Owner:  NLM     Status:  MEDLINE    
Eosinophils are multi-functional leucocytes that play a role in inflammatory processes including allergy and infection. Although bone marrow (BM) inflammatory cells are the main source of eosinophil-basophil (Eo/B) differentiation-inducing cytokines, a recent role has been demonstrated for cytokine induction through Toll-like receptor (TLR)-mediated signalling in BM progenitors. Having previously demonstrated that cord blood (CB) progenitors induce Eo/B colony-forming units (CFU) after lipopolysaccharide (LPS) stimulation, we sought to investigate the intracellular mechanisms by which LPS induces Eo/B differentiation. Freshly isolated CD34-enriched human CB cells were stimulated with LPS (and/or pharmacological inhibitors) and assessed for alterations in haematopoietic cytokine receptor expression and signalling pathways by flow cytometry, Eo/B CFU in methylcellulose cultures, and cytokine secretion using Luminex assays. The LPS stimulation resulted in a significant increase in granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive, as opposed to interleukin-5-responsive, Eo/B CFU, which also correlated with significant increases in CD34(+) cell GM-CSFRα expression. Functionally, CB CD34(+) cells secrete abundant amounts of GM-CSF following LPS stimulation, via a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism; this secretion was responsible for Eo/B CFU formation ex vivo, as shown by antibody blockade. We show for the first time that LPS stimulation of CB progenitor cells results in autocrine activation of p38 MAPK-dependent GM-CSF secretion facilitating Eo/B differentiation ex vivo. This work provides evidence that early life exposure to products of bacterial agents can modulate Eo/B differentiation, representing a novel mechanism by which progenitor cells can respond to microbial stimuli and so affect immune and inflammatory responses.
Pia Reece; Adrian J Baatjes; Michael M Cyr; Roma Sehmi; Judah A Denburg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-24     Completed Date:  2013-07-01     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  256-64     Citation Subset:  IM    
Copyright Information:
© 2013 Blackwell Publishing Ltd.
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MeSH Terms
Antigens, CD34 / immunology,  metabolism
Autocrine Communication / drug effects,  immunology
Basophils / cytology,  immunology*
Cell Differentiation / drug effects,  immunology*
Colony-Forming Units Assay
Eosinophils / cytology,  immunology*
Fetal Blood / cytology
Granulocyte-Macrophage Colony-Stimulating Factor / immunology,  metabolism,  pharmacology
Hematopoietic Stem Cells / drug effects,  immunology,  metabolism
Interleukin-5 / immunology,  pharmacology
Lipopolysaccharides / immunology,  pharmacology
Phosphorylation / drug effects,  immunology
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / immunology,  metabolism
Toll-Like Receptor 4 / agonists,  immunology*,  metabolism
p38 Mitogen-Activated Protein Kinases / immunology,  metabolism
Reg. No./Substance:
0/Antigens, CD34; 0/CSF2RA protein, human; 0/Interleukin-5; 0/Lipopolysaccharides; 0/Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; 0/Toll-Like Receptor 4; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor; EC Mitogen-Activated Protein Kinases

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

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