The adhesive sickle erythrocyte: cause and consequence of abnormal interactions with endothelium, monocytes/macrophages and model membranes

Abstract

The sickle RBC has a distinct propensity for abnormal adherence to vascular endothelial cells, monocytes, macrophages and aminophospholipid liposomes. Sickle RBC adherence to endothelium may be due to aberrant electrostatic forces, with a major contribution coming from factors in the RBC's plasma environment. The abnormal translocation of aminophospholipids in sickle RBC membranes has been implicated in their adherence to monocytes and liposomes. Abnormal interactions with macrophages (adherence and erythrophagocytosis) may be due to abnormal amounts of IgG on the sickle RBC surface and/or modification of the RBC membrane by dialdehyde byproducts of lipid peroxidation. However, the RBC membrane is an exceedingly complex structure, and these various abnormalities may well be highly interrelated. On the other hand, it is also possible that different abnormalities may be responsible for different cell-cell interactions. Precise identification of the adhesive factor(s) of the sickle RBC membrane will require additional investigation. Regardless of the mechanism(s) involved, data suggest that propensity for adherence of RBC to endothelial cells may correlate with clinical vaso-occlusive severity, perhaps helping to explain not only heterogeneity among patients but also temporal variability in disease severity for individual patients. Likewise, the abnormal adherence of sickle RBCs to monocytes/macrophages may help explain the attenuated survival of sickle RBCs.