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Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2301-2309
Neuropilin-1 Is Expressed on Bone Marrow Stromal Cells: A Novel
Interaction With Hematopoietic Cells?
Rafaèle Tordjman,
Nathalie Ortéga,
Laure Coulombel,
Jean Plouët,
Paul-Henri Roméo, and
Valérie Lemarchandel
From INSERM U474, Hopital Henri Mondor, Créteil, France;
Laboratoire de Biologie Moléculaire Eucaryote, CNRS UPR 9006, Toulouse, France; and INSERM U363, IGR, Villejuif, France.
In adult bone marrow, hematopoietic stem cells are found in close
association with distinctive stromal cell elements. This association is
necessary for maintenance of hematopoiesis, but the precise mechanisms
underlying the cross-talk between stromal cells and hematopoietic stem
cells are poorly understood. In this study, we used a bone marrow
stromal cell line (MS-5) that is able to support human long-term
hematopoiesis. This hematopoietic-promoting activity cannot be related
to expression of known cytokines and is abolished by addition of
hydrocortisone. Using a gene trap strategy that selects genes encoding
transmembrane or secreted proteins expressed by MS-5 cells, we obtained
several insertions that produced fusion proteins. In one clone, fusion
protein activity was downregulated in the presence of hydrocortisone,
and we show that insertion of the trap vector has occurred into the
neuropilin-1 gene. Neuropilin-1 is expressed in MS-5 cells, in other
hematopoietic-supporting cell lines, and in primary stromal cells but
not in primitive hematopoietic cells. We show that neuropilin-1 acts as
a functional cell-surface receptor in MS-5 cells. Two neuropilin-1
ligands, semaphorin III and VEGF 165, can bind to these cells, and the addition of VEGF 165 to MS-5 cells increases expression of 2 cytokines known to regulate early hematopoiesis, Tpo and Flt3-L. Finally, we show
that stromal cells and immature hematopoietic cells express different
neuropilin-1 ligands. We propose that neuropilin-1 may act as a novel
receptor on stromal cells by mediating interactions between stroma and
primitive hematopoietic cells.

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