|
|
Previous Article | Table of Contents | Next Article 
Vascular cell adhesion molecule-1 is involved in mediating hypoxia- induced
sickle red blood cell adherence to endothelium: potential role in sickle
cell disease
BN Setty and MJ Stuart
Division of Pediatric Hematology-Oncology, St Christopher's Hospital for
Children, Philadelphia, PA 19134-1095, USA.
We investigated the effects of hypoxia on red blood cell (RBC)- endothelial
cell (EC) adherence and the potential mechanism(s) involved in mediating
this effect. We report that hypoxia significantly increased sickle RBC
adherence to aortic EC when compared with the normoxia controls. However,
hypoxia had no effect on the adherence of normal RBCs. In additional
studies, we found that the least dense sickle RBCs containing CD36+ and
VLA-4+ reticulocytes were involved in hypoxia-induced adherence. We next
evaluated the effects of hypoxia on the expression of EC surface receptors
involved in RBC adherence to macrovascular ECs, including vascular cell
adhesion molecule-1 (VCAM- 1), intracellular adhesion molecule-1 (ICAM-1),
and the vitronectin receptor (VnR). Hypoxia upregulated the expression of
both VCAM-1 and ICAM-1, whereas no effect on VnR was noted. Potential
involvement of VCAM-1 and ICAM-1 in mediating hypoxia-induced sickle RBC-EC
adhesion was next investigated using monoclonal antibodies against these
receptors. Whereas anti-VCAM-1 had no effect on basal adherence, it
inhibited hypoxia-induced sickle RBC adherence in a concentration-
dependent manner, with 50% to 75% inhibition noted at 10 to 60
micrograms/mL antibody (n = 6, P < .05 to P < .01). Anti-ICAM-1 (10
to 60 micrograms/mL, n = 8) had no effect on either basal or hypoxia-
induced adherence. As noted in the bovine aortic ECs, hypoxia stimulated
the adherence of sickle RBCs to human retinal capillary ECs, and this
response appeared to be mediated via mechanisms similar to those observed
with macro-endothelium, ie, via the adhesive receptor combination
VCAM-1-VLA-4. Our studies show that hypoxia enhances sickle RBC adhesion to
both macrovascular and human microvascular ECs via the adhesive receptor
VCAM-1. Our findings are of interest because hypoxia is an integral part of
the pathophysiology of the vaso-occlusive phenomenon in sickle cell anemia.
Volume 88,
Issue 6,
pp. 2311-2320,
09/15/1996
Copyright © 1996 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:

|
 |

|
 |
 
G. J. Kato and M. T. Gladwin
Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell Vasculopathy
JAMA,
December 10, 2008;
300(22):
2638 - 2646.
[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]
|
 |
|

|
 |

|
 |
 
K. I. Ataga, C. G. Moore, C. A. Hillery, S. Jones, H. C. Whinna, D. Strayhorn, C. Sohier, A. Hinderliter, L. V. Parise, and E. P. Orringer
Coagulation activation and inflammation in sickle cell disease-associated pulmonary hypertension
Haematologica,
January 1, 2008;
93(1):
20 - 26.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M.-P. Wautier, W. El Nemer, P. Gane, J.-D. Rain, J.-P. Cartron, Y. Colin, C. Le Van Kim, and J.-L. Wautier
Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin {alpha}5 chain and Lu/BCAM
Blood,
August 1, 2007;
110(3):
894 - 901.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Haynes Jr., B. Obiako, J. A. King, R. B. Hester, and S. Ofori-Acquah
Activated neutrophil-mediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells
Am J Physiol Heart Circ Physiol,
October 1, 2006;
291(4):
H1679 - H1685.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. G. Woodside, R. M. Kram, J. S. Mitchell, T. Belsom, M. J. Billard, B. W. McIntyre, and P. Vanderslice
Contrasting Roles for Domain 4 of VCAM-1 in the Regulation of Cell Adhesion and Soluble VCAM-1 Binding to Integrin {alpha}4beta1.
J. Immunol.,
April 15, 2006;
176(8):
5041 - 5049.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. D. Belcher, H. Mahaseth, T. E. Welch, A. E. Vilback, K. M. Sonbol, V. S. Kalambur, P. R. Bowlin, J. C. Bischof, R. P. Hebbel, and G. M. Vercellotti
Critical role of endothelial cell activation in hypoxia-induced vasoocclusion in transgenic sickle mice
Am J Physiol Heart Circ Physiol,
June 1, 2005;
288(6):
H2715 - H2725.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Jison, P. J. Munson, J. J. Barb, A. F. Suffredini, S. Talwar, C. Logun, N. Raghavachari, J. H. Beigel, J. H. Shelhamer, R. L. Danner, et al.
Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease
Blood,
July 1, 2004;
104(1):
270 - 280.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. H. Schwartz, C. A. White, and B. A. Freeman
Do we kNOw how HSP90 and eNOS mediate lung injury in sickle cell disease?
Am J Physiol Lung Cell Mol Physiol,
April 1, 2004;
286(4):
L701 - L704.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. S. Kean, E. A. Manci, J. Perry, C. Balkan, S. Coley, D. Holtzclaw, A. B. Adams, C. P. Larsen, L. L. Hsu, and D. R. Archer
Chimerism and cure: hematologic and pathologic correction of murine sickle cell disease
Blood,
December 15, 2003;
102(13):
4582 - 4593.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Wei, J. M. Runnels, and C. P. Lin
Selective Uptake of Indocyanine Green by Reticulocytes in Circulation
Invest. Ophthalmol. Vis. Sci.,
October 1, 2003;
44(10):
4489 - 4496.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Perelman, S. K. Selvaraj, S. Batra, L. R. Luck, A. Erdreich-Epstein, T. D. Coates, V. K. Kalra, and P. Malik
Placenta growth factor activates monocytes and correlates with sickle cell disease severity
Blood,
August 15, 2003;
102(4):
1506 - 1514.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. J. Zuzak, M. T. Gladwin, R. O. Cannon III, and I. W. Levin
Imaging hemoglobin oxygen saturation in sickle cell disease patients using noninvasive visible reflectance hyperspectral techniques: effects of nitric oxide
Am J Physiol Heart Circ Physiol,
August 7, 2003;
285(3):
H1183 - H1189.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V Mak and S C Davies
The pulmonary physician in critical care * Illustrative case 6: Acute chest syndrome of sickle cell anaemia
Thorax,
August 1, 2003;
58(8):
726 - 728.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A K Siddiqui and S Ahmed
Pulmonary manifestations of sickle cell disease
Postgrad. Med. J.,
July 1, 2003;
79(933):
384 - 390.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. T. Gladwin, A. N. Schechter, F. P. Ognibene, W. A. Coles, C. D. Reiter, W. H. Schenke, G. Csako, M. A. Waclawiw, J. A. Panza, and R. O. Cannon III
Divergent Nitric Oxide Bioavailability in Men and Women With Sickle Cell Disease
Circulation,
January 21, 2003;
107(2):
271 - 278.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. G. T. VI, D. C. Tang, S. A. Savage, S. F. Leitman, S. I. Heller, G. R. Serjeant, G. P. Rodgers, and S. J. Chanock
Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease
Blood,
December 15, 2002;
100(13):
4303 - 4309.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M K. Mathews, D S McLeod, C Merges, J Cao, and G A Lutty
Neutrophils and leucocyte adhesion molecules in sickle cell retinopathy
Br J Ophthalmol,
June 1, 2002;
86(6):
684 - 690.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. N. Y. Setty, S. Kulkarni, and M. J. Stuart
Role of erythrocyte phosphatidylserine in sickle red cell-endothelial adhesion
Blood,
March 1, 2002;
99(5):
1564 - 1571.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B.A. Diwan, M.T. Gladwin, C.T. Noguchi, J.M. Ward, A.L. Fitzhugh, and G.S. Buzard
Renal Pathology in Hemizygous Sickle Cell Mice
Toxicol Pathol,
February 1, 2002;
30(2):
254 - 262.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
N. M. Matsui, L. Borsig, S. D. Rosen, M. Yaghmai, A. Varki, and S. H. Embury
P-selectin mediates the adhesion of sickle erythrocytes to the endothelium
Blood,
September 15, 2001;
98(6):
1955 - 1962.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. A. Lutty, M. Taomoto, J. Cao, D. S. McLeod, P. Vanderslice, B. W. McIntyre, M. E. Fabry, and R. L. Nagel
Inhibition of TNF-{{alpha}}-induced Sickle RBC Retention in Retina by a VLA-4 Antagonist
Invest. Ophthalmol. Vis. Sci.,
May 1, 2001;
42(6):
1349 - 1355.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
B. N. Y. Setty, S. Kulkarni, C. D. Dampier, and M. J. Stuart
Fetal hemoglobin in sickle cell anemia: relationship to erythrocyte adhesion markers and adhesion
Blood,
May 1, 2001;
97(9):
2568 - 2573.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Kurozawa and Y. Nasu
Circulating Adhesion Molecules in Patients with Vibration-Induced White Finger
Angiology,
December 1, 2000;
51(12):
1003 - 1006.
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Molinas and P. R. Koninckx
Hypoxaemia induced by CO2 or helium pneumoperitoneum is a co-factor in adhesion formation in rabbits
Hum. Reprod.,
August 1, 2000;
15(8):
1758 - 1763.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Harlan
Introduction: anti-adhesion therapy in sickle cell disease
Blood,
January 15, 2000;
95(2):
365 - 367.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. De Franceschi, C. Brugnara, P. Rouyer-Fessard, H. Jouault, and Y. Beuzard
Formation of Dense Erythrocytes in SAD Mice Exposed to Chronic Hypoxia: Evaluation of Different Therapeutic Regimens and of a Combination of Oral Clotrimazole and Magnesium Therapies
Blood,
December 15, 1999;
94(12):
4307 - 4313.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Stuart and B.N. Y. Setty
Sickle Cell Acute Chest Syndrome: Pathogenesis and Rationale for Treatment
Blood,
September 1, 1999;
94(5):
1555 - 1560.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Willam, R. Schindler, U. Frei, and K.-U. Eckardt
Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells
Am J Physiol Heart Circ Physiol,
June 1, 1999;
276(6):
H2044 - H2052.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Sultana, Y. Shen, V. Rattan, C. Johnson, and V. K. Kalra
Interaction of Sickle Erythrocytes With Endothelial Cells in the Presence of Endothelial Cell Conditioned Medium Induces Oxidant Stress Leading to Transendothelial Migration of Monocytes
Blood,
November 15, 1998;
92(10):
3924 - 3935.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. B. Cines, E. S. Pollak, C. A. Buck, J. Loscalzo, G. A. Zimmerman, R. P. McEver, J. S. Pober, T. M. Wick, B. A. Konkle, B. S. Schwartz, et al.
Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders
Blood,
May 15, 1998;
91(10):
3527 - 3561.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. L. YUNG, R. N. CHANNICK, P. F. FEDULLO, W. R. AUGER, K. M. KERR, S. W. JAMIESON, D. P. KAPELANSKI, and K. M. MOSER
Successful Pulmonary Thromboendarterectomy in Two Patients with Sickle Cell Disease
Am. J. Respir. Crit. Care Med.,
May 1, 1997;
157(5):
1690 - 1693.
[Abstract]
[Full Text]
|
 |
|
|
|