Download Fluorescence Intensity Fluorescence Intensity

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1123
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Fluorescence Intensity
Fig 1. Fas expression in marrow mononuclear cells of a normal
individual and a patient with MDS. Phycoerytherin-conjugatedmurine anti-human Far lgGl (PharMingen, San Diego, CA) was used to
identify Far expression on bone marrow cells by flow cytometry.
Data are representativeof findingsin four RA patients; in one
patient,
only a minimal increase in Fas expressionwas observed.
stained for Fas than did control samples. This was particularly true
for CD34+ cells (78% 2 18% for MDS, v 33% 2 11% for normal
cells) as determined by double staining.
If apoptosis is mediated via Fas, interactions with an agonistic
ligand must occur. Indeed, there was a significant increase in FasLigand expression on marrow cells from MDS patients (37.6% 2
12.3%) compared with normal individuals (21.1% % 7.4%; n = 8)
(Fig 2). The implications of our findings are crucial if interactions
of Fas and Fas-Ligand are responsible for initiating apoptosis. Particularly with cell membrane-associated Fas-Ligand, apoptosis
might be expected to occur in Fas-positive "clusters" of cells (as
observed by Bogdanovic et al)4 adjacent to other cells expressing
Fas-Ligand.
Our findings in a small number of patients further complement
the proposed model that Fas and Fas-Ligand are involved in the
inhibition of normal hematopoiesis in patients with MDS. The event
responsible for the development of MDS is generally not known. It
is possible that the release of regulators such as TNF-a, TGF-P,
interferon-y, or others yet to be determined results in upregulation
not only of Fas, but also of Fas-Ligand. Alternatively, MDS cells,
in the process of their evolution, may spontaneously upregulate Fas,
Fas-Ligand, or both, or may show increased responsiveness to exogenous regulators thereby facilitating upregulation. Current studies
are aimed at further characterizing, both phenotypically and functionally, cells that express either Fas, Fas-Ligand, or both.
Geoffrey M. Gersuk
Jong W. Lee
Cassandra A. Beckham
Jeanne Anderson
H. Joachim Deeg
Fluorescence Intensity
Fig 2. Far-Ligand expression in marrow mononuclear cells ofa
normal individual and a patient with MDS. Affinity-purified rabbit
anti-human Fas-Ligand polyclonal antibody (Santa Crur Biotechnology, Santa Cruz, CA) was used to identify Fas-Ligand expressionon
bone marrow cells by flow cytometry. The depicted pattern was seen
in three RA patients; in two patients, only a moderate increase in
Fas Ligand expressionwas observed.
Fred Hutchinson Cancer Research Center
University of Washington
Seattle, WA
REFERENCES
1. Philpot NJ, Scopes J, Marsh JCW, Gordon-Smith EC, Gibson
FM: Increased apoptosis in aplastic anemia bone marrow progenitor
cells: Possible pathophysiologic significance. Exp Hematol23:1642,
1995
2. Raza A, Gezer S, Mundle S, Gao X-Z, Alvi S, Borok R, Rifkin
S, Iftikhar A, Shetty V, Parcharidou A, h e w J, Marcus B, Khan Z,
Chaney C, Showel J, Gregory S, F'reislerH: Apoptosis in bone
marrow biopsy samples involving stromal and hematopoietic cells
in 50 patients with myelodysplastic syndromes. Blood 86:268, 1995
3. Hatake K, Tomizuka H, Ikeda M, Tsunoda JI, Hoshino Y,
Ostsuki T, Tasahara T, Yonehara S, Miura Y: The presence of
apoptosis in refractory anemia of myelodysplasia, in Abraham NG
(ed): Molecular Biology of Haematopoiesis, v01 3. Andover, MD,
Intercept, 1994, p 127
4. Bogdanovic AD, Jankovic GM, Colovic MD, Trpinac DP,
Bumbasirevic VZ: Apoptosis inbonemarrow of myelodysplastic
syndrome patients. Blood 87:3064, 1996 (letter)
5. Maciejewski JP, Selleri C, Sato T, Anderson S, Young NS:
Increased expression of Fas antigen on bone marrow CD34' cells
of patients with aplastic anemia. Br J Haematol 91:245, 1995
6. Maciejewski JP, Selleri C, Anderson S, Young NS: Fas antigen
expression on CD34' human marrow cells is induced by interferon
y and tumor necrosis factor a and potentiates cytokine-mediated
hematopoietic suppression in vitro. Blood 85:3183, 1995
From www.bloodjournal.org by guest on August 9, 2017. For personal use only.
1996 88: 1123-1125
Growth of Epstein-Barr virus-associated B-lymphoproliferative
disease tissue in a severe combined immunodeficient mouse [letter]
SM Perera, I Johannessen, JA Thomas, LA Brooks, JN Jobe, DH Crawford, R Radley- Smith and
M Phillips
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