Renin–angiotensin system expression in rat bone marrow haematopoietic and stromal cells

Abstract

The existence of a bone marrow renin–angiotensin system (RAS) is evidenced by the association of renin, angiotensin converting enzyme (ACE), and angiotensin (Ang) II and its AT₁ and AT₂ receptors with both normal and disturbed haematopoiesis. The expression of RAS components by rat unfractionated bone marrow cells (BMC), haematopoietic-lineage BMC and cultured marrow stromal cells (MSC) was investigated to determine which specific cell types may contribute to a local bone marrow RAS. The mRNAs for angiotensinogen, renin, ACE, and AT_1a and AT₂ receptors were present in BMC and in cultured MSC; ACE2 mRNA was detected only in BMC. Two-colour flow fluorocytometry analysis showed immunodetectable angiotensinogen, ACE, AT₁ and AT₂ receptors, and Ang II, as well as binding of Ang II to AT₁ and AT₂ receptors, in CD4⁺, CD11b/c⁺, CD45R⁺ and CD90⁺ BMC and cultured MSC; renin was found in all cell types with the exception of CD4⁺ BMC. Furthermore, Ang II was detected by radioimmunoassay in MSC homogenates as well as conditioned culture medium. The presence of Ang II receptors in both haematopoietic-lineage BMC and MSC, and the de novo synthesis of Ang II by MSC suggest a potential autocrine–paracrine mechanism for local RAS-mediated regulation of haematopoiesis.