Inhibition of neutrophil function by PPAR-γ is mediated via HIF-1α signaling. Annexin V–depleted peripheral blood neutrophils isolated from HDs were used in the study. (A) Effects of the PPAR-γ antagonist GW9662 on chemotaxis, calcium mobilization, and respiratory burst activities of neutrophils exposing to hypoxic conditions, and western blot analysis of protein extracts using antibodies against HIF-1α, PPAR-γ, or β-actin. Three independent experiments were conducted with similar results. ○, normoxia; ●, hypoxia; ▾, hypoxia and PPAR-γ antagonist GW9662. (B) Effects of the PPAR-γ antagonist GW9662 on chemotaxis, calcium mobilization, and respiratory burst activities of neutrophils exposed to the hypoxia mimetic CoCl_2, and western blot analysis of protein extracts using antibodies against HIF-1α, PPAR-γ, or β-actin. Three independent experiments were conducted with similar results. ○, control; ●,CoCl₂; ▾, CoCl₂ and PPAR-γ antagonist GW9662. (C) Effects of HIF-α inhibitor 2-ME2 on chemotaxis, calcium mobilization, and respiratory burst activities of neutrophils exposed to hypoxic conditions, and western blot analysis of protein extracts using antibodies against HIF-1α, PPAR-γ or β-actin. Three independent experiments were conducted with similar results. ○, normoxia; ●, hypoxia; ▾, hypoxia and 2-ME2. Chemotaxis was examined in response to 10⁻⁷ M fMLP. Data represent the mean ± SEM. Calcium mobilization was examined in response to 10⁻⁷ M fMLP. Representative profiles are shown. Respiratory burst was examined in response to PMA. Representative profiles are shown. **P < .005, *P < .05.