Formyl peptide receptor 1 up-regulation and formyl peptide receptor 2/3 down-regulation of blood immune cells along with defective lipoxin A4/resolvin D1 production in obstructive sleep apnea patients

BACKGROUND: This study aims to investigate the role of FPR 1/2/3 expressions in patients with obstructive sleep apnea (OSA). METHOD: We made cross-sectional comparisons of FPR1/2/3 expressions of blood neutrophil, M1/M2a monocyte, and natural killer (NK) cell between 16 healthy subjects (HS), 16 primary snoring (PS) subjects, 46 treatment-naive OSA patients, and 18 severe OSA patients under long-term continuous positive airway pressure treatment (severe OSA on CPAP). RESULTS: FPR1 expressions on neutrophil were increased in treatment-naive OSA and severe OSA on CPAP groups versus either HS or PS. FPR2 expressions on neutrophil were decreased in treatment-naive OSA versus HS, and returned to normal in severe OSA on CPAP group. FPR1/FPR2 expression ratio on neutrophil was increased in treatment-naive OSA versus either HS or PS. Serum lipoxin A4, resolvin D1 levels, and FPR3 expressions of M1, M2a and NK cells were all decreased in treatment-naive OSA versus HS. OSA patients with hypertension had decreased FPR2 expressions on neutrophil and FPR3 expressions of NK cell. FPR1 expression, FPR1/FPR2 expression ratio on neutrophil, and FPR3 expression of M1 cell were all reversed after > 6-month CPAP treatment in 9 selected patients. In vitro intermittent hypoxia with re-oxygenation treatment in THP-1 cells resulted in increased FPR1/FPR2 expression ratio of M1 cells, and increased FPR1/FPR3 expression ratio of M2a cells. CONCLUSIONS: FPR1 over-expression and insufficiency of FPR2 and FPR3 in association with defective lipoxin A4 and resolving D1 production were associated with disease severity of OSA and its adverse consequences.