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Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells

Hypertension and Vascular Disease Center Wake Forest University School of Medicine Winston-Salem, NC, USA

E Ann Tallant

Hypertension and Vascular Disease Center Wake Forest University School of Medicine Winston-Salem, NC, USA

Patricia E Gallagher

Hypertension and Vascular Disease Center Wake Forest University School of Medicine Winston-Salem, NC, USA

Carlos M Ferrario

Hypertension and Vascular Disease Center Wake Forest University School of Medicine Winston-Salem, NC, USA

William B Strawn

Hypertension and Vascular Disease Center Wake Forest University School of Medicine Winston-Salem, NC, USA, bstrawn{at}wfubmc.edu

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.

Key Words: angiotensin II • arachidonic acid • marrow • stromal • haematopoiesis

Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 4, 176-182 (2004)
DOI: 10.3317/jraas.2004.037


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