Delayed neutrophil apoptosis in patients with sleep apnea

被引:102
作者
Dyugovskaya, Larissa [1 ]
Polyakov, Andrey [1 ]
Lavie, Peretz [1 ]
Lavie, Lena [1 ]
机构
[1] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Unit Anat & Cell Biol, Lloyd Rigler Sleep Apnea Res Lab, IL-31096 Haifa, Israel
关键词
obstructive sleep apnea; polymorphonuclear leukocytes; apoptosis; adhesion molecules; atherosclerosis;
D O I
10.1164/rccm.200705-675OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Rationale: Obstructive sleep apnea (OSA), characterized by intermittent hypoxia/reoxygenation (IHR), is associated with atherosclerosis. Polymorphonuclear leukocytes (PMNs) are implicated in atherogenesis by producing oxidizing radicals and proteolytic enzymes during IPMN-endothelium interactions. PMN apoptosis is a fundamental, injury-limiting mechanism, which prevents their destructive potential. Objectives: To determine whether PMN apoptosis and expression of adhesion molecules are affected by OSA and IHR in vitro. Methods: Apoptosis and expression of adhesion molecules were assessed in whole blood PMNs by flow cytometry, verified by various culture conditions, and morphology. These were complemented by exposing whole blood and purified PMNs to IHR and to sustained hypoxia in vitro. Measurements and Main Results: This study demonstrates for the first time that, in patients with moderate to severe OSA, PMN apoptosis is delayed. Apoptosis was attenuated in patients with an apnea-hypopnea index (AHI) of more than 15, determined by decreased expression of low-CD16/annexin-V-positive PMNs, by lowered caspase-3 activity and nuclear condensation. Concomitantly, selectin-CD15 expression was increased in a severity-dependent manner in patients with moderate to severe OSA having an AHI greater than 15. The percentage of apoptotic PMNs was negatively correlated with OSA severity, determined by AHI, and positively with CD15 expression. In nasal continuous positive airway pressure-treated patients, CD15 expression was attenuated and low CD16 was increased, whereas omitting nasal continuous positive airway pressure for a single night increased CD15 expression and decreased the percentage of low CD16. IHR in vitro delayed PMN apoptosis as well. Conclusions: Decreased apoptosis and increased expression of adhesion molecules were noted in OSA PMNs. Although adhesion molecules may facilitate increased PMN-endothelium interactions, decreased apoptosis may further augment these interactions and facilitate free radical and proteolytic enzyme release.
引用
收藏
页码:544 / 554
页数:11
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