|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1749-1756
Resistance of Paroxysmal Nocturnal Hemoglobinuria Cells to the
Glycosylphosphatidylinositol-Binding Toxin Aerolysin
Robert A. Brodsky,
Galina L. Mukhina,
Kim L. Nelson,
Tracy S. Lawrence,
Richard J. Jones, and
J. Thomas Buckley
From the Johns Hopkins Oncology Center, Baltimore, MD; and the
Department of Biochemistry and Microbiology, University of Victoria,
Victoria, British Columbia, Canada.
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell
disorder caused by a somatic mutation of the PIGA gene. The product of
this gene is required for the biosynthesis of
glycosylphosphatidylinositol (GPI) anchors; therefore, the phenotypic
hallmark of PNH cells is an absence or marked deficiency of all
GPI-anchored proteins. Aerolysin is a toxin secreted by the bacterial
pathogen Aeromonas hydrophila and is capable of killing target
cells by forming channels in their membranes after binding to
GPI-anchored receptors. We found that PNH blood cells (erythrocytes,
lymphocytes, and granulocytes), but not blood cells from normals or
other hematologic disorders, are resistant to the cytotoxic effects of
aerolysin. The percentage of lysis of PNH cells after aerolysin
exposure paralleled the percentage of CD59+ cells in the
samples measured by flow cytometry. The kinetics of red blood cell
lysis correlated with the type of PNH erythrocytes. PNH type III cells
were completely resistant to aerolysin, whereas PNH type II cells
displayed intermediate sensitivity. Importantly, the use of aerolysin
allowed us to detect PNH populations that could not be detected by
standard flow cytometry. Resistance of PNH cells to aerolysin allows
for a simple, inexpensive assay for PNH that is sensitive and
specific. Aerolysin should also be useful in studying PNH biology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. A. Brodsky
How I treat paroxysmal nocturnal hemoglobinuria
Blood,
June 25, 2009;
113(26):
6522 - 6527.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Dingli, L. Luzzatto, and J. M. Pacheco
Neutral evolution in paroxysmal nocturnal hemoglobinuria
PNAS,
November 25, 2008;
105(47):
18496 - 18500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Brodsky
Narrative Review: Paroxysmal Nocturnal Hemoglobinuria: The Physiology of Complement-Related Hemolytic Anemia
Ann Intern Med,
April 15, 2008;
148(8):
587 - 595.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Brodsky
Paroxysmal Nocturnal Hemoglobinuria: Stem Cells and Clonality
Hematology,
January 1, 2008;
2008(1):
111 - 115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Sugimori, T. Chuhjo, X. Feng, H. Yamazaki, A. Takami, M. Teramura, H. Mizoguchi, M. Omine, and S. Nakao
Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia
Blood,
February 15, 2006;
107(4):
1308 - 1314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Brodsky
New Insights into Paroxysmal Nocturnal Hemoglobinuria
Hematology,
January 1, 2006;
2006(1):
24 - 28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Parker, M. Omine, S. Richards, J.-i. Nishimura, M. Bessler, R. Ware, P. Hillmen, L. Luzzatto, N. Young, T. Kinoshita, et al.
Diagnosis and management of paroxysmal nocturnal hemoglobinuria
Blood,
December 1, 2005;
106(12):
3699 - 3709.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Beier, S. Balabanov, T. Buckley, K. Dietz, U. Hartmann, M. Rojewski, L. Kanz, H. Schrezenmeier, and T. H. Brummendorf
Accelerated telomere shortening in glycosylphosphatidylinositol (GPI)-negative compared with GPI-positive granulocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) detected by proaerolysin flow-FISH
Blood,
July 15, 2005;
106(2):
531 - 533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Hu, G. L. Mukhina, S. Piantadosi, J. P. Barber, R. J. Jones, and R. A. Brodsky
PIG-A mutations in normal hematopoiesis
Blood,
May 15, 2005;
105(10):
3848 - 3854.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S Krauss
Laboratory Diagnosis of Paroxysmal Nocturnal Hemoglobinuria
Ann. Clin. Lab. Sci.,
October 1, 2003;
33(4):
401 - 406.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Wang, T. Chuhjo, S. Yasue, M. Omine, and S. Nakao
Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome
Blood,
December 1, 2002;
100(12):
3897 - 3902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Sotgia, B. Razani, G. Bonuccelli, W. Schubert, M. Battista, H. Lee, F. Capozza, A. L. Schubert, C. Minetti, J. T. Buckley, et al.
Intracellular Retention of Glycosylphosphatidyl Inositol-Linked Proteins in Caveolin-Deficient Cells
Mol. Cell. Biol.,
June 1, 2002;
22(11):
3905 - 3926.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Nelson and J. T. Buckley
Channel Formation by the Glycosylphosphatidylinositol-anchored Protein Binding Toxin Aerolysin Is Not Promoted by Lipid Rafts
J. Biol. Chem.,
June 23, 2000;
275(26):
19839 - 19843.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Abrami, M. Fivaz, T. Kobayashi, T. Kinoshita, R. G. Parton, and F. G. van der Goot
Cross-talk between Caveolae and Glycosylphosphatidylinositol-rich Domains
J. Biol. Chem.,
August 10, 2001;
276(33):
30729 - 30736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
