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Bone marrow stroma in humans: anti-nerve growth factor receptor antibodies
selectively stain reticular cells in vivo and in vitro
G Cattoretti, R Schiro, A Orazi, D Soligo and MP Colombo
Divisione di Anatomia Patologica e Citologia, Istituto Nazionale per lo
Studio e la Cura dei Tumori, Milano, Italy.
Two anti-nerve growth factor receptor (LNGFR or p75NGFR) antibodies, Me20.4
and Me8211, label stromal cells with dendritic features in fresh smears and
in formalin-fixed, paraffin-embedded human bone marrow (BM). The LNGFR+
cells have an oval nucleus, a scanty cytoplasm with long dendrites that
intermingle with the hematopoietic cells, line the abluminal side of sinus
endothelial cells, and provide the scaffold for the hematopoietic marrow.
At the electron microscopy level, the immunogold tag labels the body and
the long branching dendrites of fibroblast-like cells with scanty cytoplasm
containing mitochondria, endoplasmic reticulum, and dense bodies. The
LNGFR+ cells are positive for alkaline phosphatase, reticulin, collagen
III, vimentin, TE-7, and CD13 but negative for endothelial (vWF, CD34,
Pal-E), neural (CD56, neurofilament) and leukocyte markers (CD45, CD68).
The LNGFR+ stromal cells appear in the fetal BM before the hematopoietic
activity begins, originate from the vessel adventitia, and radiate in the
Bm cavity. Long-term BM culture (LTBMC) in vitro contain LNGFR+ stromal
cells. We document the presence of RNA message for the low- (LNGFR) and the
high- affinity NGF receptor (NTRK1) by using RT-PCR on fresh BM aspirate
and on LTBMC. BM biopsies from patients with hematologic fibrogenic
diseases and in cytokine-treated cancer patients are evaluated for LNGFR+
cells: the amount of stained cells is correlated with the traditional
reticulin stain in cases of myelofibrosis, therapy-related myelodysplasia,
leukemia, and detected an increase of stromal cells in cytokine-treated
patients. The anti-LNGFR antibodies represent a specific membrane marker
for the adventitial reticular cells (ARC) of the human marrow and allow
precise evaluation and quantitation of this important BM microenvironment
component in vivo and in vitro.
Volume 81,
Issue 7,
pp. 1726-1738,
04/01/1993
Copyright © 1993 by The American Society of Hematology

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