Noncanonical Mechanisms for Direct Bone Marrow Generating Ang II (Angiotensin II) Predominate in CD68 Positive Myeloid Lineage Cells

Bone marrow (BM) Ang II (angiotensin II) is a major participant in the regulation of hematopoiesis and immunity. The novel tissue substrate Ang-(1–12) [angiotensin-(1–12)] and its cleaving enzyme chymase are an essential source of Ang II production in cardiac tissue. We hypothesized this noncanonical chymase-mediated Ang II–producing mechanism exists in the BM tissue. Immunohistostaining and flow cytometry confirmed the presence of Ang-(1–12) immunoreaction in the BM of SD (Sprague Dawley) rats. Chymase-mediated Ang II–producing activity in BM was ≈1000-fold higher than ACE (angiotensin-converting enzyme)-mediated Ang II–producing activity (4531±137 and 4.2±0.3 fmol/min per mg, respectively; n=6; P