Supplemental Digital Content is available in the text. 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<0.001) and 280-fold higher than chymase activity in the left ventricle of 16.3±1.7 fmol/min per mg (P<0.001). Adding a selective chymase inhibitor, TEI-F00806, eliminated almost all 125I-Ang II production. Flow cytometry demonstrated that delta median fluorescence intensity of chymase in cluster of differentiation 68 positive cells was significantly higher than that in cluster of differentiation 68 negative cells (1546±157 and 222±48 arbitrary units, respectively; P=0.0021). Cluster of differentiation 68 positive and side scatter low subsets, considered to be myeloid progenitors, express the highest chymase fluorescence intensity in rat BM. Chymase activity and cellular expression was similar in both male and female rats. In conclusion, myeloid lineage cells, especially myeloid progenitors, have an extraordinary Ang II–producing activity by chymase in the BM.

中文翻译：

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CD68 阳性骨髓谱系细胞中直接骨髓生成 Ang II（血管紧张素 II）的非典型机制占主导地位


文本中提供了补充数字内容。骨髓 (BM) Ang II（血管紧张素 II）是造血和免疫调节的主要参与者。新型组织底物 Ang-(1–12) [血管紧张素-(1–12)] 及其裂解酶食糜酶是心脏组织中 Ang II 产生的重要来源。我们假设这种非典型的食糜酶介导的 Ang II 产生机制存在于 BM 组织中。免疫组织染色和流式细胞术证实 SD (Sprague Dawley) 大鼠的 BM 中存在 Ang-(1–12) 免疫反应。 BM 中食糜酶介导的 Ang II 生成活性比 ACE（血管紧张素转换酶）介导的 Ang II 生成活性高约 1000 倍（分别为每毫克 4531±137 和 4.2±0.3 fmol/min；n=6 ；P<0.001)，比左心室食糜酶活性 16.3±1.7 fmol/min/mg (P<0.001) 高 280 倍。添加选择性食糜酶抑制剂 TEI-F00806 几乎消除了所有 125I-Ang II 的产生。流式细胞术显示分化68阳性细胞簇中食糜酶的荧光强度中值Delta显着高于分化68阴性细胞簇（分别为1546±157和222±48任意单位；P=0.0021）。分化簇68个阳性和侧向散射低亚群，被认为是骨髓祖细胞，在大鼠BM中表达最高的食糜酶荧光强度。雄性和雌性大鼠的食糜酶活性和细胞表达相似。总之，骨髓谱系细胞，尤其是骨髓祖细胞，通过骨髓中的食糜酶具有非凡的产生血管紧张素II的活性。