|
|
 Previous Article | Table of Contents | Next Article 
Membrane Phospholipid Asymmetry in Human Thalassemia
Frans A. Kuypers,
Jie Yuan,
Rachel A. Lewis,
L. Michael Snyder,
Charles R. Kiefer,
Ahnond Bunyaratvej,
Suthat Fucharoen,
Lisa Ma,
Lori Styles,
Kitty de Jong, and
Stanley L. Schrier
From the Children's Hospital Oakland Research Institute, Oakland,
CA; Stanford University, Stanford, CA; University of Massachusetts
Medical Center, Worcester, MA; Ramathibodi Hospital, Bangkok, Thailand;
and the Siriraj Hospital Bangkok, Thailand.
Phospholipid asymmetry in the red blood cell (RBC)
lipid bilayer is well maintained during the life of the cell, with
phosphatidylserine (PS) virtually exclusively located in the inner
monolayer. Loss of phospholipid asymmetry, and consequently exposure of
PS, is thought to play an important role in red cell pathology. The
anemia in the human thalassemias is caused by a combination of
ineffective erythropoiesis (intramedullary hemolysis) and a decreased
survival of adult RBCs in the peripheral blood. This premature
destruction of the thalassemic RBC could in part be due to a loss of
phospholipid asymmetry, because cells that expose PS are recognized and
removed by macrophages. In addition, PS exposure can play a role in the hypercoagulable state reported to exist in severe  -thalassemia intermedia. We describe PS exposure in RBCs of 56 comparably anemic patients with different genetic backgrounds of the  - or
-thalassemia phenotype. The use of fluorescently labeled annexin V
allowed us to determine loss of phospholipid asymmetry in individual
cells. Our data indicate that in a number of thalassemic patients,
subpopulations of red cells circulate that expose PS on their outer
surface. The number of such cells can vary dramatically from patient to patient, from as low as that found in normal controls (less than 0.2%)
up to 20%. Analysis by fluorescent microscopy of -thalassemic RBCs indicates that PS on the outer leaflet is distributed either over
the entire membrane or localized in areas possibly related to regions
rich in membrane-bound -globin chains. We hypothesize that these
membrane sites in which iron carrying globin chains accumulate and
cause oxidative damage, could be important in the loss of membrane
lipid organization. In conclusion, we report the presence of
PS-exposing subpopulations of thalassemic RBC that are most likely
physiologically important, because they could provide a surface for
enhancing hemostasis as recently reported, and because such exposure
may mediate the rapid removal of these RBCs from the circulation,
thereby contributing to the anemia.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 3044-3051
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Sipahi, A. Kara, A. Kuybulu, Y. Egin, and N. Akar
Congenital Thrombotic Risk Factors in {beta}-Thalassemia
Clinical and Applied Thrombosis/Hemostasis,
October 1, 2009;
15(5):
581 - 584.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. Srinoun, S. Svasti, W. Chumworathayee, J. Vadolas, P. Vattanaviboon, S. Fucharoen, and P. Winichagoon
Imbalanced globin chain synthesis determines erythroid cell pathology in thalassemic mice
Haematologica,
September 1, 2009;
94(9):
1211 - 1219.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Mohandas and P. G. Gallagher
Red cell membrane: past, present, and future
Blood,
November 15, 2008;
112(10):
3939 - 3948.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Bernaudin, S. Verlhac, S. Chevret, M. Torres, L. Coic, C. Arnaud, A. Kamdem, I. Hau, M. Grazia Neonato, and C. Delacourt
G6PD deficiency, absence of {alpha}-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia
Blood,
November 15, 2008;
112(10):
4314 - 4317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. V. Libani, E. C. Guy, L. Melchiori, R. Schiro, P. Ramos, L. Breda, T. Scholzen, A. Chadburn, Y. Liu, M. Kernbach, et al.
Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in {beta}-thalassemia
Blood,
August 1, 2008;
112(3):
875 - 885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. N. Y. Setty and S. G. Betal
Microvascular endothelial cells express a phosphatidylserine receptor: a functionally active receptor for phosphatidylserine-positive erythrocytes
Blood,
January 15, 2008;
111(2):
905 - 914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Minetti, L. Agati, and W. Malorni
The microenvironment can shift erythrocytes from a friendly to a harmful behavior: Pathogenetic implications for vascular diseases
Cardiovasc Res,
July 1, 2007;
75(1):
21 - 28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Stoyanova, M. Trudel, H. Felfly, D. Garcia, and G. Cloutier
Characterization of circulatory disorders in {beta}-thalassemic mice by noninvasive ultrasound biomicroscopy
Physiol Genomics,
March 14, 2007;
29(1):
84 - 90.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Kuypers
Membrane Lipid Alterations in Hemoglobinopathies
Hematology,
January 1, 2007;
2007(1):
68 - 73.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Lang and K. Kerr
Risk Factors for Chronic Thromboembolic Pulmonary Hypertension
Proceedings of the ATS,
September 1, 2006;
3(7):
568 - 570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X Jais, V Ioos, C Jardim, O Sitbon, F Parent, A Hamid, E Fadel, P Dartevelle, G Simonneau, and M Humbert
Splenectomy and chronic thromboembolic pulmonary hypertension
Thorax,
December 1, 2005;
60(12):
1031 - 1034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mandal, A. Mazumder, P. Das, M. Kundu, and J. Basu
Fas-, Caspase 8-, and Caspase 3-dependent Signaling Regulates the Activity of the Aminophospholipid Translocase and Phosphatidylserine Externalization in Human Erythrocytes
J. Biol. Chem.,
November 25, 2005;
280(47):
39460 - 39467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Gallagher, S. H. Chang, M. P. Rettig, J. E. Neely, C. A. Hillery, B. D. Smith, and P. S. Low
Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis
Blood,
June 1, 2003;
101(11):
4625 - 4627.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. H. K. Chui, S. Fucharoen, and V. Chan
Hemoglobin H disease: not necessarily a benign disorder
Blood,
February 1, 2003;
101(3):
791 - 800.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Littera, G. La Nasa, G. Derchi, M. D. Cappellini, C. Y. P. Chang, and L. Contu
Long-term treatment with oral sildenafil in a thalassemic patient with pulmonary hypertension
Blood,
July 30, 2002;
100(4):
1516 - 1517.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Valles, M. T. Santos, J. Aznar, M. Martinez, A. Moscardo, M. Pinon, M. J. Broekman, and A. J. Marcus
Platelet-erythrocyte interactions enhance alpha IIbbeta 3 integrin receptor activation and P-selectin expression during platelet recruitment: down-regulation by aspirin ex vivo
Blood,
May 13, 2002;
99(11):
3978 - 3984.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. V. Tyulina, V. D. Prokopieva, R. D. Dodd, J. R. Hawkins, S. W. Clay, D. O. Wilson, A. A. Boldyrev, and P. Johnson
IN VITRO EFFECTS OF ETHANOL, ACETALDEHYDE AND FATTY ACID ETHYL ESTERS ON HUMAN ERYTHROCYTES
Alcohol Alcohol.,
March 1, 2002;
37(2):
179 - 186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Eldor and E. A. Rachmilewitz
The hypercoagulable state in thalassemia
Blood,
January 1, 2002;
99(1):
36 - 43.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. de Jong, S. K. Larkin, L. A. Styles, R. M. Bookchin, and F. A. Kuypers
Characterization of the phosphatidylserine-exposing subpopulation of sickle cells
Blood,
August 1, 2001;
98(3):
860 - 867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. G. Blankenberg, L. Naumovski, J. F. Tait, A. M. Post, and H. W. Strauss
Imaging Cyclophosphamide-Induced Intramedullary Apoptosis in Rats Using 99mTc-Radiolabeled Annexin V
J. Nucl. Med.,
February 1, 2001;
42(2):
309 - 316.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
B. N. Y. Setty, S. Kulkarni, A. K. Rao, and M. J. Stuart
Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation
Blood,
August 1, 2000;
96(3):
1119 - 1124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Manodori, G. A. Barabino, B. H. Lubin, and F. A. Kuypers
Adherence of phosphatidylserine-exposing erythrocytes to endothelial matrix thrombospondin
Blood,
February 15, 2000;
95(4):
1293 - 1300.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. de Jong, S. K. Larkin, S. Eber, P. F.H. Franck, B. Roelofsen, and F. A. Kuypers
Hereditary Spherocytosis and Elliptocytosis Erythrocytes Show a Normal Transbilayer Phospholipid Distribution
Blood,
July 1, 1999;
94(1):
319 - 325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
