Abstract
Acute chest syndrome (ACS) of sickle cell disease (SCD) is characterized pathologically by vaso-occlusive processes that result from abnormal interactions between sickle red blood cells (RBCs), white blood cells (WBCs) and/or platelets, and the vascular endothelium. One potential mechanism of vascular damage in ACS is by generation of oxygen-related molecules, such as superoxide (O2-), hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and the hydroxyl (•OH) radical. The present review summarizes the evidence for alterations in oxidant stress during ACS of SCD, and the potential contributions of RBCs, WBCs and the vascular endothelium to this process.
Highlights
Acute chest syndrome (ACS) is an important cause of morbidity and mortality in sickle cell disease (SCD), occurring in up to 45% of patients and recurring in up to 80% of those afflicted [1,2]
We review the role of each of these cell types in the generation of oxygen radicals, and the effects that these molecules have on cellular metabolism in SCD
Endothelin-1 transcription may be induced by activation of the redox-sensitive nuclear factor-κB (NF-κB) or activating protein (AP)-1 by reactive oxygen radicals generated during ACS [12]. These findings suggest that, in addition to direct toxicity to the vascular endothelium, reactive oxygen species may contribute to vaso-occlusion through alteration in vascular tone
Summary
ACS is an important cause of morbidity and mortality in SCD, occurring in up to 45% of patients and recurring in up to 80% of those afflicted [1,2]. We observed a ninefold increase in the plasma levels of F2 isoprostanes, a stable marker of lipid peroxidation, in the plasma of ACS patients as compared with that of normal volunteers (Klings ES et al, unpublished data) These findings suggest, both in humans and in mouse models of SCD, that there is increased oxidative burden and that alterations in the redox state may play a role in the development of vaso-occlusion. Exposure to ACS plasma resulted in a decreased level of the endothelial cell antioxidant thiols [36] These findings suggest that, in SCD patients, during ACS, there is a decreased capacity to scavenge free radicals, making such persons more susceptible to oxidant-related damage. Further work is needed to elucidate the role of homocysteine in vaso-occlusion
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