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Blood, 15 December 2001, Vol. 98, No. 13, pp. 3784-3792
NEOPLASIA
Expression, epitope analysis, and functional role of the LFA-2
antigen detectable on neoplastic mast cells
Gerit-Holger Schernthaner,
John-Hendrik Jordan,
Minoo Ghannadan,
Hermine Agis,
Dorian Bevec,
Rosa Nuñez,
Luis Escribano,
Otto Majdic,
Martin Willheim,
Christof Worda,
Dieter Printz,
Gerhard Fritsch,
Klaus Lechner, and
Peter Valent
From the Department of Internal Medicine I, Division of
Hematology & Hemostaseology, Institute of Immunology, Institute of
Pathophysiology, Department of Obstetrics and Gynecology, Division of
Gynecological Endocrinology and Reproductive Medicine, University of
Vienna, Austria; Axxima Pharmaceuticals, Martinsried, Germany;
Servicio de Hematologia, Mast Cell Unit, Hospital Ramón y Cajal,
University of Alcalá de Henares, Madrid, Spain; and St Anna
Children's Hospital, Vienna, Austria.
Recent data suggest that mast cells (MCs) in patients with systemic
mastocytosis or mast cell leukemia express a CD2-reactive antigen.
To explore the biochemical nature and function of this antigen, primary
MCs as well as the MC line HMC-1 derived from a patient with mast cell
leukemia were examined. Northern blot experiments revealed
expression of CD2 messenger RNA in HMC-1, whereas primary nonneoplastic
MCs did not express transcripts for CD2. In cell surface staining
experiments, bone marrow (BM) MCs in systemic mastocytosis (n = 12)
as well as HMC-1 cells (30%-80%) were found to express the T11-1 and
T11-2 (but not T11-3) epitopes of CD2. By contrast, BM MCs in
myelodysplastic syndromes and nonhematologic disorders (bronchiogenic
carcinoma, foreskin phimosis, uterine myeomata ) were consistently
CD2 . All MC species analyzed including HMC-1 were found
to express LFA-3 (CD58), the natural ligand of CD2. To study the
functional role of CD2 on neoplastic MCs, CD2+ and
CD2 HMC-1 cells were separated by cell sorting.
CD2+ HMC-1 cells were found to form spontaneous aggregates
and rosettes with sheep erythrocytes in excess over CD2
cells, and a T11-1 antibody inhibited both the aggregation and rosette
formation. Moreover, exposure of CD2+ HMC-1 cells to T11-1
or T11-2 antibody was followed by expression of T11-3. In addition,
stimulation of neoplastic MCs through T11-3 and a second CD2 epitope
resulted in histamine release. These data show that neoplastic MCs
express functionally active CD2. It is hypothesized that expression of
CD2 is associated with pathologic accumulation and function of MCs in
systemic mastocytosis.
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