Neuropilin-1 is expressed on bone marrow stromal cells: A novel interaction with hematopoietic cells?

In adult bone marrow, hematopoietic stem cells are found in close associati on with distinctive stromal cell elements, This association is necessary fo r maintenance of hematopoiesis, but the precise mechanisms underlying the c ross-talk between stromal cells and hematopoietic stem cells are poorly und erstood. In this study, we used a bone marrow stromal cell line (MS-5) that is able to support human long-term hematopoiesis, This hematopoietic-promo ting activity cannot be related to expression of known cytokines and is abo lished by addition of hydrocortisone. Using a gene trap strategy that selec ts genes encoding transmembrane or secreted proteins expressed by MS-5 cell s, we obtained several insertions that produced fusion proteins. In one clo ne, fusion protein activity was downregulated in the presence of hydrocorti sone, and we show that insertion the trap vector has occurred into the neur opilin-1 gene. Neuropilin-1 is expressed in MS-5 cells, in other hematopoie tic-supporting cell lines, and in primary stromal cells but not in primitiv e hematopoietic cells. We show that neuropilin-1 acts as a functional cell- surface receptor in MS-5 cells, Two neuropilin-1 ligands, semaphorin III an d VEGF 165, can bind to these cells, and the addition of VEGF 165 to MS-5 c ells increases expression of 2 cytokines known to regulate early hematopoie sis, Tpo and Flt3-L. Finally, we show that stromal cells and immature hemat opoietic cells express different neuropilin-1 ligands. We propose that neur opilin-1 may act as a novel receptor on stromal cells by mediating interact ions between stroma and primitive hematopoietic cells. (C) 1999 by The Amer ican Society of Hematology.