The angiotensin-converting enzyme (ACE) has been proposed as a marker of cells involved in haematopoiesis and myelopoiesis/differentiation. The purpose of this study was to assess the role of ACE in haematopoietic progenitor cell (HPC) mobilization in response to the pro-inflammatory cytokine granulocyte-colony stimulating factor (G-CSF).

ACE was expressed in bone marrow cells in murine bone and in cells lining the endosteal bone which are morphologically similar to osteoblasts. HPC mobilization (G-CSF, 5 days) in wild-type and ACE^-/- mice was quantified by assaying the ability of peripheral blood mononuclear cells to form colonies after 14 days in culture or in vivo in spleens from wild-type mice after 12 days. ACE^-/- mice displayed significantly more colonies in both assays. ACE inhibition in wild-type mice reproduced the ACE^-/- mice mobilization phenotype. Moreover, mobilization after cross over bone marrow transplantation showed increased number of CFU-Cs in ACE^-/- mice reconstituted with wild-type bone marrow, suggesting a niche dependent influence.

ACE has previously been identified as a signalling molecule and is phosphorylated following stimulation with an ACE inhibitor resulting in JNK activation. We therefore generated a transgenic mouse lacking the phosphorylation site. Also in this mouse mobilization of HPCs was greater than in wild-type mice. Interestingly, we found that thein vivoadministration of G-CSF elicited the serine phosphorylation of ACE (Ser1270) and thus potentially activated the "ACE-signalling" pathway.

These findings indicate a new role for ACE in the bone marrow niche and in progenitor cell function which is possibly mediated by G-CSF induced ACE signalling.