title: Airway epithelial cells release eosinophil survival-promoting factors (GM-CSF) after stimulation of proteinase-activated receptor 2.
abstract: BACKGROUND
  Epithelium is considered an active participant in allergic inflammation. Proteinase-activated receptor (PAR) 2 is expressed in a variety of cell types, including epithelial cells, and has been implicated in inflammation.
  
  
  OBJECTIVE
  PAR-2-mediated activation of airway epithelial cells induces the release of mediators that could promote eosinophil survival and mediate eosinophil recruitment.
  
  
  METHODS
  PAR-2-activating peptides were used to activate the human airway epithelial cell line A549, as well as primary cultures of small airway epithelial cells (SAECs). Human peripheral blood eosinophils were cultured in the presence or absence of epithelial cell supernatants. Survival was assessed by using an Annexin V apoptosis detection kit. GM-CSF and eotaxin were measured by using ELISA.
  
  
  RESULTS
  Eosinophils undergo apoptosis in the absence of growth factors. Supernatants from PAR-2-activated A549 epithelial cells increased eosinophil survival. Supernatants from resting SAECs also increased eosinophil survival, but supernatants from PAR-2-activated SAECs showed a greater effect. The effect of PAR-2-activated epithelial cell supernatants on eosinophil survival was completely inhibited by a neutralizing anti-GM-CSF antibody but not an anti-IL-5 antibody. Resting A549 cells did not release any detectable GM-CSF, whereas PAR-2-activated cells released 35 pg/10(6) cells. Resting SAECs released 754.3 pg/10(6) cells of GM-CSF, which was further increased to 1360.5 pg/10(6) cells after PAR-2-mediated activation. Budesonide inhibited this PAR-2 effect. PAR-2-activated epithelial cells also released eotaxin.
  
  
  CONCLUSIONS
  PAR-2-mediated activation of airway epithelial cells induced release of GM-CSF, which promoted eosinophil survival and activation. It also induced release of eotaxin, which could mediate eosinophil recruitment to the airways.
authors: Pulmonary Research Group, Department of Medicine, 574 HMRC, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
authors: H
authors: H
authors: Vliagoftis
authors: A D
authors: AD
authors: Befus
authors: M D
authors: MD
authors: Hollenberg
authors: R
authors: R
authors: Moqbel
mesh_terms: D002460:Cell Line; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology*
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor