title: Mast Cell-Activated Bone Marrow Mesenchymal Stromal Cells Regulate Proliferation and Lineage Commitment of CD34(+) Progenitor Cells.
abstract: BACKGROUND
  Shortly after allergen exposure, the number of bone marrow (BM) and circulating CD34(+) progenitors increases. We aim to analyze the possible mechanism whereby the allergic reaction stimulates BM to release these effector cells in increased numbers. We hypothesize that mast cells (MCs) may play a predominant role in this process.
  
  
  OBJECTIVE
  To examine the effect of IgE-activated MCs on BM mesenchymal stromal cells which regulate proliferation and differentiation of CD34(+) progenitors.
  
  
  METHODS
  Primary MCs were derived from CD34(+) precursors and activated with IgE/anti-IgE. BM mesenchymal stromal cells were co-cultured with CD34(+) progenitor cells and stimulated with IL-1/TNF or IgE/anti-IgE-activated MCs in Transwell system.
  
  
  RESULTS
  BM mesenchymal stromal cells produce low level of thymic stromal lymphopoietin (TSLP) under steady state conditions, which is markedly increased by stimulation with proinflammatory cytokines IL-1 and TNF or IgE-activated MCs. The latter also triggers bone marrow-derived mesenchymal stromal cells production of G-CSF, and GM-CSF while inhibiting SDF-1. MC-activated mesenchymal stromal cells stimulate CD34(+) cells to proliferate and to regulate their expression of early allergy-associated genes.
  
  
  CONCLUSIONS
  This in vitro study indicates that IgE-activated MCs trigger BM mesenchymal stromal cells to release TSLP and hematopoietic growth factors and to regulate the proliferation and lineage commitment of CD34(+) precursor cells. The data predict that the effective inhibition of MCs should impair mobilization and accumulation of allergic effector cells and thereby reduce the severity of allergic diseases.
authors.affiliation: Laboratory on Allergy, CRCHUM Notre-Dame Hospital , Montreal, QC , Canada.
authors.forename: Zoulfia
authors.initials: Z
authors.lastname: Allakhverdi
authors.affiliation: Inflammation Research, Amgen Inc. , Seattle, WA , USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.affiliation: Center for Human Cell Therapy, Immune Disease Institute , Boston, MA , USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Armant
authors.affiliation: Department of Medicine, Allergy Division, University of Virginia , Charlottesville, VA , USA.
authors.forename: Rachana
authors.initials: R
authors.lastname: Agrawal
authors.affiliation: Department of Medicine, Allergy Division, University of Virginia , Charlottesville, VA , USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Woodfolk
authors.affiliation: Firestone Institute for Respiratory Health, McMaster University , Hamilton, ON , Canada.
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
authors.affiliation: Asthma Research Group, McMaster University , Hamilton, ON , Canada.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Howie
authors.affiliation: Asthma Research Group, McMaster University , Hamilton, ON , Canada.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.affiliation: Laboratory on Allergy, CRCHUM Notre-Dame Hospital , Montreal, QC , Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Delespesse
keywords: TSLP; Th2 response; allergic inflammation; asthma; bone marrow mesenchymal stromal cells; circulating CD34+ progenitor cells; mast cells