title: The Effect of PPAR Agonists on the Migration of Mature and Immature Eosinophils.
abstract: PPARγ agonists can either enhance or inhibit eosinophil migration, which is a sum of directional migration (chemotaxis) and random cell movement (chemokinesis). To date, the effects of PPAR agonists on chemokinesis have not been examined. This study investigates the effects of PPARα, δ, and γ agonists on eosinophil migration and chemokinesis. Eosinophils purified from blood of atopic donors were preincubated with rosiglitazone (PPARγ agonist), GW9578 (PPARα agonist), GW501516 (PPARδ agonist), or diluent. The effects of PPAR agonists were examined on eosinophil chemokinesis, eotaxin-induced migration of eosinophils, and migration of IL-5Rα+ CD34+ cells. Expressions of CCR3, phospho-p38, phospho-ERK, and calcium release were also measured in eosinophils after rosiglitazone treatment. Low concentrations of rosiglitazone, but not GW9578 or GW501516, increased chemokinesis of eosinophils (P = 0.0038), and SDF-1α-induced migration of immature eosinophils (P = 0.0538). Rosiglitazone had an effect on eosinophil calcium flux but had no effect on expression of CCR3 or phosphorylation of p38 or ERK. In contrast, high concentrations of rosiglitazone inhibited eosinophil migration (P = 0.0042). The effect of rosiglitazone on eosinophil migration and chemokinesis appears to be through modification of calcium signaling, which alludes to a novel PPAR-mediated mechanism to modulate eosinophil function.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada L8S 4K1.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Smith
authors.forename: Haruki
authors.initials: H
authors.lastname: Imaoka
authors.forename: Neha
authors.initials: N
authors.lastname: Punia
authors.forename: Anam
authors.initials: A
authors.lastname: Irshad
authors.forename: Luke L
authors.initials: LL
authors.lastname: Janssen
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau