lewis-x-antigen and Sleep-Apnea--Obstructive

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 PMN-endothelium interactions. PMN apoptosis is a fundamental, injury-limiting mechanism, which prevents their destructive potential.. To determine whether PMN apoptosis and expression of adhesion molecules are affected by OSA and IHR in vitro.. 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.. 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.. 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.

Topics: Adult; Annexin A5; Apoptosis; Caspase 3; CD11c Antigen; Continuous Positive Airway Pressure; Endothelium, Vascular; Female; Flow Cytometry; Humans; Hydrocortisone; Lewis X Antigen; Male; Middle Aged; Neutrophils; Receptors, IgG; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Time Factors

Topics: Atherosclerosis; CD11c Antigen; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Continuous Positive Airway Pressure; Endothelial Cells; Endothelium, Vascular; Humans; Hypoxia; Lewis X Antigen; Monocytes; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Free radicals and adhesion molecules were implicated in the pathogenesis of atherosclerosis leading to cardiovascular disorders. Therefore, we investigated the link between CD15, CD11c, CD11b, and CD64 expression on leukocytes and their ability to generate reactive oxygen species (ROS) in patients with OSA and control volunteers. We also studied the effects of hypoxia in vitro on monocytes from control subjects and the ability of monocytes from both groups to adhere to human endothelial cells in culture. The effect of nasal continuous positive airway pressure (nCPAP) treatment was studied as well. We found that OSA was associated with increased expression of adhesion molecules CD15 and CD11c on monocytes, increased adherence of monocytes in culture to human endothelial cells, increased intracellular ROS production in some monocyte and granulocyte subpopulations, and upregulation of CD15 expression due to hypoxia in vitro in monocytes of control subjects. Furthermore, nCPAP treatment was associated with downregulation of CD15 and CD11c monocyte expression and decreased basal ROS production in CD11c+ monocytes. Monocyte adherence to endothelial cells decreased as well. Our findings provide one of the possible mechanisms for explaining the high rate of cardiovascular morbidity in patients with sleep apnea.

Topics: Adult; Cell Adhesion; Cell Adhesion Molecules; Cell Hypoxia; Cells, Cultured; Endothelium, Vascular; Female; Granulocytes; Humans; Integrin alphaXbeta2; Leukocytes; Lewis X Antigen; Macrophage-1 Antigen; Male; Middle Aged; Monocytes; Positive-Pressure Respiration; Reactive Oxygen Species; Sleep Apnea, Obstructive