Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes.
Open Access
- 1 June 1985
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 75 (6), 1965-1972
- https://doi.org/10.1172/jci111913
Abstract
The precise mechanism by which sickle erythrocytes (RBC) are removed from the circulation is controversial, although it is possible that enhanced recognition of these cells by circulating mononuclear phagocytes could contribute to this process. We investigated this possibility by interacting sickle cells with cultured human peripheral blood monocytes. Our results show that both irreversibly sickled cells (ISC) and deoxygenated reversibly sickled cells (RSC) had a higher avidity for adherence to monocytes than did oxygenated sickle and normal RBC. ISC were the most adherent cell type. Adherence of RSC to monocytes was found to be reversible; reoxygenation of deoxygenated RSC resulted in a significant decrease in RSC--monocyte adherence. Concomitant with alterations in sickle RBC adherence were alterations in the organization and bilayer distribution of membrane phospholipids in these cells. Specifically, enhanced adherence was associated with increased exposure of RBC membrane outer leaflet phosphatidylserine (PS) and phosphatidylethanolamine, whereas lack of adherence was associated with normal patterns of membrane phospholipid distribution. To investigate the possibility of whether the exposure of PS in the outer membrane leaflet of these cells might be responsible for their recognition by monocytes, the membranes of normal RBC were enriched with the fluorescent PS analogue 1-acyl-2[(N-4-nitro-benzo-2-oxa-1,3-diazole)aminocaproyl]-phosphatidy lse rine (NBD-PS) via transfer of the exogenous lipid from a population of donor phospholipid vesicles (liposomes). RBC enriched with NBD-PS exhibited enhanced adherence to monocytes, whereas adherence of RBC enriched with similar amounts of NBD-phosphatidylcholine (NBD-PC) was not increased. Furthermore, preincubation of monocytes with PS liposomes resulted in a approximately 60% inhibition of ISC adherence to monocytes, whereas no inhibition occurred when monocytes were preincubated with PC liposomes. These findings strongly suggest that erythrocyte surface PS may be a ligand recognized by receptors on human peripheral blood monocytes and that abnormal exposure of PS in the outer leaflet of the RBC membrane, as found in sickle RBC, might serve to trigger their recognition by circulating monocytes. Our results further suggest that abnormalities in the organization of erythrocyte membrane phospholipids may have significant pathophysiologic implications, possibly including shortened cell survival.This publication has 21 references indexed in Scilit:
- Phagocytosis of sickle erythrocytes: immunologic and oxidative determinants of hemolytic anemia.1984
- Abnormalities in membrane phospholipid organization in sickled erythrocytes.JCI Insight, 1981
- Biochemical, morphological, and ultrastructural studies on the uptake of liposomes by murine macrophages.1981
- Abnormal Adherence of Sickle Erythrocytes to Cultured Vascular EndotheliumJCI Insight, 1980
- Adhesion of normal and sickle erythrocytes to endothelial monolayer cultures.1979
- Lipid Asymmetry in MembranesAnnual Review of Biochemistry, 1979
- Red cell calcium content and transmembrane calcium movements in sickle cell anemia.1977
- Irreversible deformation of the spectrin-actin lattice in irreversibly sickled cells.JCI Insight, 1976
- Abnormal rheology of oxygenated blood in sickle cell anemiaJCI Insight, 1970
- 32DFP and 51Cr for Measurement of Red Cell Life Span in Abnormal Hemoglobin SyndromesBlood, 1969