Fig 1.
Flow diagram shows the process of the patients’ selection and enrollment.
Table 1.
Demographic, biochemistry, and sleep data of all the 96 study participants.
Fig 2.
Formyl peptide receptor (FPR) 1/2/3 expressions of blood innate immune cells in patients with sleep disordered breathing and healthy subject without snoring.
(A) Increased FPR1 expression on neutrophil in patients with treatment-naive obstructive sleep apnea (OSA), and severe OSA under long-term CPAP treatment groups as compared with that in subjects with primary snoring (PS) and healthy subjects (HS). (B) Decreased FPR2 expression on neutrophil in treatment-naïve OSA group as compared with that in HS, and severe OSA on CPAP groups. (C) Increased FPR1/FPR2 expression ratio in treatment-naïve OSA and severe OSA on CPAP groups as compared with that in HS group. (D) Decreased FPR3 expression of M1 monocyte in treatment-naïve OSA and severe OSA on CPAP groups as compared with that in HS group. (E) Decreased FPR3 expression of M2a monocyte in treatment-naïve OSA versus HS group. (F) Decreased FPR3 expression of NK cell in PS, and treatment-naïve OSA, groups as compared with that in HS group. The box plots show the 25th, 50th, 75th percentiles, maximum, and minimum. *P<0.05 for comparisons between HS and another groups by Kruskal-Wallis test followed by post-hoc corrections and linear regression adjustments #p<0.05 for comparisons between PS and another groups by Kruskal-Wallis test followed by post-hoc corrections and linear regression adjustments @p<0.05 for comparisons between treatment-naïve OSA and severe OSA on CPAP groups by Kruskal-Wallis test followed by post-hoc corrections and linear regression adjustments.
Fig 3.
Correlations of FPR expressions of blood immune cells with sleep parameters.
(A) FPR1 expression on neutrophil was positively correlated with ODI. FPR1/FPR2 expression ratio was (B) negatively correlated with minimum SaO2, and positively correlated with (C) snoring index and (D) Epworth Sleepiness Scale. FPR3 expression of M1 monocyte was negatively correlated with (E) apnea hypopnea index, (F) percent time of SaO2<90%, and (G) Epworth Sleepiness Scale, and (H) positively correlated with mean SaO2.
Fig 4.
FPR1/2/3 expression changes of blood immune cells after 6-month CPAP treatment.
(A) FPR1 (+) percentage on neutrophil was decreased after > 6-month CPAP treatment. (B) FPR2 expression on neutrophil was increased after >6-month CPAP treatment. (C) FPR1/FPR2 expression ratio on neutrophil was decreased after > 6-month CPAP treatment. (D) FPR3 expression of M1 cell was increased after > 6-month CPAP treatment. The box plots show the 25th, 50th, 75th percentiles, maximum, and minimum.
Fig 5.
Serum lipoxin A4 (LXA4) and resolvin D1 (RvD1) deficiency in patients with sleep-disordered breathing.
(A) Serum RvD1 and (B) LXA4 levels were both decreased in patients with primary snoring (PS), treatment-naïve OSA, and severe OSA on CPAP treatment as compared with that in the healthy subjects (HS). (C) Serum LXA4 was negatively correlated with cell surface FPR1/FPR2 expression ratio on blood neutrophil. (D) Serum RvD1 levels were further reduced after > 6-month CPAP treatment in 9 selected OSA patients. The box plots show the 25th, 50th, 75th percentiles, maximum, and minimum. *P<0.05 for comparisons between HS and another groups by Kruskal-Wallis test followed by post-hoc corrections.
Table 2.
Summary of the positive results of the protein expressions of the three FPRs and five FPR ligands in the current study.
Fig 6.
FPR1/2/3 expressions of human monocytic THP-1 cells exposed to normoxia (NOX), 2 days of persistent hypoxia (PH), or 2 days of intermittent hypoxia with re-oxygenation (IHR).
The box plots show the 25th, 50th, 75th percentiles, maximum, and minimum. IHR treatment resulted in increased (A) FPR1 and (B) FPR2 expressions on M2a cells. Both IHR and PH treatment resulted in decreased (C) FPR1, (D) FPR2, and (E) FPR3 expressions on CD14+CD209-M1 cells. PH and IHR treatment resulted in decreased (F) FPR3 expression of CD14+Cd209+M2a cells. Both PH and IHR (G) increased FPR1/FPR2 expression ratio of M1 cell, and (H) increased FPR1/FPR3 expression ratio of M2a cell. (I) Cell viability was decreased in both PH and IHR versus NOX condition. *p<0.05 for comparisons between IHR and NOX conditions by U test #p<0.05 for comparisons between PH and NOX conditions by U test.