Document Detail


Toll-like Receptor mediated Eosinophil-Basophil Differentiation: autocrine signalling by GM-CSF in cord blood hematopoietic progenitors.
MedLine Citation:
PMID:  23347362     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Eosinophils are multi-functional leukocytes 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. Since we have previously demonstrated that cord blood (CB) progenitors induce Eo/B 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 hematopoietic cytokine receptor expression and signalling pathways by flow cytometry, Eo/B colony forming units (CFU) in methylcellulose cultures, and cytokine secretion using Luminex assays. LPS stimulation resulted in a significant increase in GM-CSF-responsive, as opposed to IL-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 MAPK-dependent mechanism; this secretion was responsible for Eo/B CFU formation ex vivo, as evidenced 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 thus affect immune and inflammatory responses. © 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
Authors:
Pia Reece; Adrian J Baatjes; Michael M Cyr; Roma Sehmi; Judah A Denburg
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Immunology     Volume:  -     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
Affiliation:
Division of Clinical Immunology & Allergy, McMaster University, Hamilton, Ontario.
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