Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

Abstract

Introduction Angiotensin II (Ang II) is recognised as a regulator of haematopoiesis, but its actions within the bone marrow are not fully understood. Support of haematopoiesis by bone marrow stromal cells (MSC) is dependent on factors that include arachidonic acid and macrophage colony stimulating factor (MCSF), both of which are increased by Ang II stimulation in other tissues. To further elucidate the mechanisms of Ang II-regulated haematopoiesis, we determined whether Ang II-stimulation alters arachidonic acid release and MCSF secretion from MSC. Methods Cynomolgus monkey MSC isolated from bone marrow aspirates and the human HS-5 stromal cell line were studied for Ang II-mediated arachidonic acid (AA) release, while secretion of MCSF in response to Ang II was studied in HS-5 cells. Cells were labelled overnight with 3H-AA and the release of 3H-AA was measured in culture medium following 20 minutes stimulation with Ang II, alone or in combination with the AT1- or AT 2-receptor antagonists, losartan and PD 123319, respectively. MCSF secretion into culture medium was measured using an enzyme immunoassay following 24 hours of treatment with Ang II alone or in combination with losartan or PD 123319. Phorbol-myristate-acetate, known to stimulate release of AA and MCSF, was used as a positive control in both experiments. Results In response to Ang II, release of 3H-AA from monkey and human MSC was increased (p<0.05) to 147±4% and 124±3% of control, respectively. The AT1- and AT2-receptor antagonists, losartan and PD 123319, individually reduced Ang II-stimulated 3H-AA release. In contrast, Ang II had no effect on secretion of MCSF from HS-5 cells. Conclusions These results provide mechanistic evidence for Ang II-mediated haematopoiesis through AA release that may, in part, explain Ang II-facilitated recovery of haematopoiesis in experimental myelosuppression and the anaemias associated with Ang II receptor blockade.

RETRACTED ARTICLE: Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro

“…It is known that these two receptors are expressed in the monkey and human HS-5 stromal cell line at the protein level [27]. Nevertheless, AT2R mRNA was not detected in human MSCs [27]. However, our study detected not only AT1R mRNA but also AT2R mRNA in cultured human bone marrow MSCs.…”

“…It is known that these two receptors are expressed in the monkey and human HS-5 stromal cell line at the protein level [27]. Nevertheless, AT2R mRNA was not detected in human MSCs [27].…”

A Role for Angiotensin II Type 1 Receptors on Bone Marrow-Derived Cells in the Pathogenesis of Angiotensin II–Dependent Hypertension

“…For example, Ang II has been shown to trigger arachidonic acid release from bone marrow cells via AT 1 and AT 2 receptor–mediated pathways. 36 We, therefore, quantitated urinary excretion of prostaglandin E 2 and prostacyclin by ELISA in the Ang II-infused BMWT and BMKO groups (n=14 per group). We found that urinary prostaglandin E 2 (2663±297 versus 2988±404 pg per 24 hours; P value not significant) and prostacyclin (10 321 ±1177 versus 11 643±2097 pg per 24 hours; P value not significant) were similar in the BMWT and BMKO groups, suggesting that differential generation of vasodilatory prostaglandins did not contribute to the enhanced blood pressure elevation in the Ang II-infused BMKO group.…”

Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil

“…These studies suggest a fundamental role of AT 1 receptor activation in atherogenesis 31. In the pursuit of the mechanism accounting for the actions of Ang II in atherogenesis, we found that early activation of monocytes occurred through upregulation of the bone marrow renin-angiotensin system, whereby hypercholesterolemia stimulates the expression of bone marrow CD11b (+) receptors in monocytes 32–34…”