Bilirubin induces loss of membrane lipids and exposure of phosphatidylserine in human erythrocytes |
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Authors: | Brito M A Silva R F M Brites D |
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Institution: | (1) Centro de Patogénese Molecular, Faculdade de Farmácia, University of Lisbon, Lisbon, Portugal |
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Abstract: | Unconjugated bilirubin increasingly binds to erythrocytes as the bilirubin-to-albumin molar ratio exceeds unity, leading to
toxic manifestations that can culminate in cell lysis. Our previous studies showed that bilirubin induces the release of lipids
from erythrocyte membranes. In the present work, those studies were extended in order to characterize the alterations of membrane
lipid composition and evaluate whether bilirubin leads to a loss of phospholipid asymmetry. To this end, human erythrocytes
were incubated with several bilirubin-to-albumin molar ratios (0.5 to 5), and cholesterol as well as the total and the individual
classes of phospholipids were determined. To detect erythrocytes with phosphatidylserine at the outer surface, the number
of annexin V-positive cells was determined following incubation with bilirubin, fixing its molar ratio to albumin at 3. The
results demonstrate profound changes in erythrocyte membrane composition, including modified cholesterol and phospholipid
content. The release of membrane cholesterol, as well as of total and individual classes of phospholipids at molar ratios
≥1, indicates that damage of erythrocytes may occur in severely ill jaundiced neonates. The loss of the inner-located phospholipids,
phosphatidylethanolamine and phosphatidylserine, points to a redistribution of phospholipids in the membrane bilayer. This
was confirmed by the exposure of phosphatidylserine at the outer cell surface. In conclusion, this study demonstrates that
bilirubin induces loss of membrane lipids and externalization of phosphatidylserine in human erythrocytes. These features
may facilitate hemolysis and erythrophagocytosis, thus contributing to enhanced bilirubin production and anemia during severe
neonatal hyperbilirubinemia.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | erythrocytes lipids membrane phospholipid asymmetry toxicity unconjugated bilirubin |
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