Loss of Membrane Components in the Pathogenesis of Antibody-Induced Spherocytosis

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Abstract
The infusion of hyperimmune agglutinating antibodies into man or animals causes spherocytosis and hemolysis. The mechanism of spherocytosis was studied in rats given rabbit anti-rat red cell antiserum intravenously. During the 18 hr after antibody infusion, a time before the onset of reticulocytosis, hematocrits fell from 40.6 to 27.6%. However, no change occurred in mean cell volume, mean cell hemoglobin content, or the red cell concentrations of potassium or adenosine triphosphate (ATP). There was a progressive loss of membrane constituents and membrane surface area which followed first order kinetics. At 18 hr membrane cholesterol had decreased 23.5%, phospholipid 26.3%, protein 4.7%, and surface area (calculated from a measure of osmotic fragility) 14.2%. There was no change in the per cent composition of the various phospholipids. Similar changes occurred in animals splenectomized before receiving antibody.These studies demonstrate that spherocytosis induced by heterologous agglutinating antibodies in vivo results from a loss of surface area with no accompanying change in cell volume or in the concentration of the major intracellular constituents. It is caused by a process acting at the cell surface leading to the loss of lipid-rich, protein-poor components of the red cell membrane.