Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes

R. S. Schwartz, Y. Tanaka, I. J. Fidler, D. T. Chiu, B. Lubin, A. J. Schroit

Research output: Contribution to journalArticle

131 Citations (Scopus)

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 deoxyygenated 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 memrane 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]-phosphatidylseri ne (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 moncoytes, 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 ~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.

Original languageEnglish (US)
Pages (from-to)1965-1972
Number of pages8
JournalJournal of Clinical Investigation
Volume75
Issue number6
StatePublished - 1985

Fingerprint

Phosphatidylserines
Monocytes
Erythrocytes
Phospholipids
Liposomes
Membranes
Erythrocyte Membrane
Phagocytes
Cultured Cells
Cell Survival
Cell Membrane
Ligands
Lipids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Schwartz, R. S., Tanaka, Y., Fidler, I. J., Chiu, D. T., Lubin, B., & Schroit, A. J. (1985). Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes. Journal of Clinical Investigation, 75(6), 1965-1972.

Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes. / Schwartz, R. S.; Tanaka, Y.; Fidler, I. J.; Chiu, D. T.; Lubin, B.; Schroit, A. J.

In: Journal of Clinical Investigation, Vol. 75, No. 6, 1985, p. 1965-1972.

Research output: Contribution to journalArticle

Schwartz, RS, Tanaka, Y, Fidler, IJ, Chiu, DT, Lubin, B & Schroit, AJ 1985, 'Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes', Journal of Clinical Investigation, vol. 75, no. 6, pp. 1965-1972.
Schwartz, R. S. ; Tanaka, Y. ; Fidler, I. J. ; Chiu, D. T. ; Lubin, B. ; Schroit, A. J. / Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes. In: Journal of Clinical Investigation. 1985 ; Vol. 75, No. 6. pp. 1965-1972.
@article{38c5fd0c457f471bb507b91870aadc1a,
title = "Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes",
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 deoxyygenated 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 memrane 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]-phosphatidylseri ne (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 moncoytes, 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 ~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.",
author = "Schwartz, {R. S.} and Y. Tanaka and Fidler, {I. J.} and Chiu, {D. T.} and B. Lubin and Schroit, {A. J.}",
year = "1985",
language = "English (US)",
volume = "75",
pages = "1965--1972",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes

AU - Schwartz, R. S.

AU - Tanaka, Y.

AU - Fidler, I. J.

AU - Chiu, D. T.

AU - Lubin, B.

AU - Schroit, A. J.

PY - 1985

Y1 - 1985

N2 - 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 deoxyygenated 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 memrane 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]-phosphatidylseri ne (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 moncoytes, 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 ~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.

AB - 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 deoxyygenated 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 memrane 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]-phosphatidylseri ne (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 moncoytes, 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 ~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.

UR - http://www.scopus.com/inward/record.url?scp=0021930709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021930709&partnerID=8YFLogxK

M3 - Article

C2 - 4008648

AN - SCOPUS:0021930709

VL - 75

SP - 1965

EP - 1972

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -