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Free access | 10.1172/JCI109646

Abnormal Adherence of Sickle Erythrocytes to Cultured Vascular Endothelium: POSSIBLE MECHANISM FOR MICROVASCULAR OCCLUSION IN SICKLE CELL DISEASE

Robert P. Hebbel, Osamu Yamada, Charles F. Moldow, Harry S. Jacob, James G. White, and John W. Eaton

Hematology Sections, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Hematology Sections, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Find articles by Hebbel, R. in: JCI | PubMed | Google Scholar

Hematology Sections, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Hematology Sections, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Find articles by Yamada, O. in: JCI | PubMed | Google Scholar

Hematology Sections, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Hematology Sections, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Find articles by Moldow, C. in: JCI | PubMed | Google Scholar

Hematology Sections, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Hematology Sections, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Find articles by Jacob, H. in: JCI | PubMed | Google Scholar

Hematology Sections, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Hematology Sections, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Find articles by White, J. in: JCI | PubMed | Google Scholar

Hematology Sections, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Hematology Sections, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Find articles by Eaton, J. in: JCI | PubMed | Google Scholar

First published January 1, 1980 - More info

Published in Volume 65, Issue 1 on January 1, 1980
J Clin Invest. 1980;65(1):154–160. https://doi.org/10.1172/JCI109646.
© 1980 The American Society for Clinical Investigation
First published January 1, 1980 - Version history
Abstract

The abnormal shape and poor deformability of the sickled erythrocyte (RBC) have generally been held responsible for the microvascular occlusions of sickle cell disease. However, there is no correlation between the clinical severity of this disease and the presence of sickled RBC. In searching for additional factors that might contribute to the pathophysiology of sickle cell disease, we have investigated the possibility that sickle RBC might be less than normally repulsive of the vascular endothelium. After RBC suspensions are allowed to settle onto plates of cultured human endothelial cells, normal RBC are completely removed by as few as six washes. In contrast, sickle RBC remain adherent despite multiple washes. On subconfluent culture plates, normal RBC are distributed randomly, whereas sickle RBC cluster around endothelial cells. Sickle RBC adherence is not enhanced by deoxygenation but does increase with increasing RBC density. The enzymatic removal of membrane sialic acid greatly diminishes the adherence of sickle RBC to endothelial cells, suggesting that sialic acid participates in this abnormal cell-cell interaction. Although net negative charge appears normal, sickle RBC mainfest an abnormal clumping of negative surface charge as demonstrated by localization of cationized ferritin. These abnormalities are reproduced in normal RBC loaded with nonechinocytogenic amounts of calcium. We conclude that sickle RBC adhere to vascular endothelial cells in vitro, perhaps caused by a calcium-induced aberration of membrane topography. This adherence may be a pathogenetic factor in the microvascular occlusions characteristic of sickle cell disease.

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