Effects of deficiencies of glycophorins C and D on the physical properties of the red cell

Abstract

Red cells of the rare Leach phenotype lack the membrane glycophorins C and D, and a proportion of the red cells are elliptocytes. Judging from tests on suspensions of red cell ghosts sheared rotationally in an ektacytometer, it has previously been suggested that these membranes are relatively fragile and poorly deformable. We have carried out analyses of individual red cells to investigate possible factors which underlie the physical changes in these glycophorin-deficient cells. Micropipette analysis of the red cell membrane showed that the rigidity and viscosity were normal, both for elliptocytes and discocytes, for three donors deficient in glycophorins C and D. Red cell transit times through 5 microns pores, measured electronically for 2000 individual cells, showed no differences from controls. It was confirmed that the index of deformation obtained using an ektacytometer was reduced, but our results suggest that this arises from shape rather than membrane changes. The elliptocytes were found to have a lower volume and surface area than discocytes from the same donor (measured by micropipette aspiration of single red cells), and were rarely found in less dense red cell fractions. No reticulocytes were found to be elliptical. These data suggest that the elliptocytes are older red cells, and are formed from red cells which are initially released into the circulation with normal shape. Their elongated shape might arise from permanent distortion of the unstable membrane by shear forces in the circulation.

Abnormal erythrocyte band 4.1 protein in myelodysplastic syndrome with elliptocytosis

“…These results indicate that the primary molecular defect in the patient's cells lines in band 4.1, which is synthesized in cells derived from the abnormal erythroid clone. It has been generally accepted that band 4.1 plays a functionally important role in maintaining erythrocyte shape and regulating membrane material properties, possibly through the regulation of spectrin-actin interaction as well as its interaction with glycophorin C. It has also been suggested that the content of glycophorin C on membranes is regulated by its association with band 4.1 (Reid et al, 1990). Erythrocytes that lack glycophorin C are known to exhibit elliptocytic morphology and also decreased membrane deformability and mechanical stability.…”

“…In hereditary elliptocytosis (HE), many cases with a defective self-association of spectrin dimer to tetramer have been reported, and molecular lesions of spectrin have been identified in several of them. Abnormality or deficiency of band 4.1 has also been found in limited cases with HE (Tchernia et al, 1981;Garbarz et al, 1984: Morle et al, 1985McGuire et al, 1988), and rare glycophorin C deficiency is known to represent asymptomatic HE (Anstee et al, 1984;Nash et al, 1990).…”

Actin Protofilament Orientation at the Erythrocyte Membrane

“…Glycophorin C is not, in contrast, retained in 4.1-deficient cell skeletons (Reid et al, 1990). However, glycophorin C-deficient membranes have near-normal elasticity (Nash et al, 1990), despite evidence for a slight deficiency of protein 4.1 (Alloisio et al, 1993). Finally, given the fact that actin is held to have simultaneous interactions with spectrin, perhaps the lipid bilayer (Pradhan et al, 1991), as well as many other proteins in the red cell (e.g., adducin; Mische et al, 1987), it could be that these latter interactions also strongly influence actin orientation.…”

Extra- and Intracellular Mechanisms of Changes in Erythrocyte Aggregation

“…These negative charges exposed on the outer surface of the erythrocyte membrane seem to be responsible for maintaining erythrocytes in the nonaggregated state [25,26]. Diminishing these charges by chemical removal of sialic acids with trypsin or neuraminidase noticeably increases EA [27].…”