Vascular cell adhesion molecule-1 (CD 106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilizationby granulocyte colony-stimulating factor

Mobilized progenitor cells currently represent the most commonly used sourc e of hematopoietic progenitor cells (HPCs) to effect hematopoietic reconsti tution following myeloalblative chemotherapies. Despite their widespread us e, the molecular mechanisms responsible for the enforced egress of HPCs fro m the bone marrow (BM) into the circulation in response to mobilizing agent s such as cytokines remain to be determined. Results of this study indicate that expression of vascular cell adhesion molecule-11 (VCAM-1) is strongly reduced in vivo in the BM during HPC mobilization by granulocyte colony-st imulating factor (G-CSF) and stem cell factor. Two serine proteases, namely , neutrophil elastase and cathepsin G, were identified, which cleave VCAM-1 and are released by neutrophils accumulating in the BM during the course o f immobilization induced by G-CSF. The proposal is made that an essential s tep contributing to the mobilization of HPCs is the proteolytic cleavage of VCAM-1 expressed by BM stromal cells, an event triggered by the degranulat ion of neutrophils accumulating in the BM in response to the administration of G-CSF. (C) 2001 by The American Society of Hematology.