Mechanisms underlying protection by AS RBS against falciparum malaria. Parasitization of AS RBCs causes increased oxygen consumption, a decrease in pO₂, and sickle hemoglobin polymerization. The membranes of these cells are further modified by oxidant stress, resulting in uptake by macrophages, impaired parasite growth and development, and decreased adherence to endothelium. Parisitization of AS RBCs leads to a decrease in the display of knobs of the cell surface along with uneven distribution. It is likely, though unproven, that hypoxia-induced sickling would aggravate this abnormal topology and further weaken interactions between the parasite protein PfEMP-1 and cognate receptors on endothelial cells, such as ICAM-1 in the brain.