Effect of angiotensin II on hematopoietic progenitor cell proliferation

Angiotensin II (AII) induced the proliferation of hematopoietic progenitor cells (HPC) isolated from murine bone marrow or human cord blood. The forma tion of colonies with more than 50 cells increased approximately five-seven fold in cultures of murine lineage-negative (Lin(-)) bone marrow cells both in the presence (day 10) and absence (day 13) of colony-stimulating factor s (CSF), This could be blocked with addition of Losartan, an antagonist of AIITR1. The increase in proliferation of early hematopoietic progenitors (L in(-)Sca I+ cells) by AII was approximately threefold and occurred only in the presence of CSF, suggesting that AII may affect mesenchymal stromal cel ls to induce CSF production and might directly affect early WC. These in vi tro studies were replicated with human HPC isolated from cord blood. AII al so accelerated the proliferation and formation of colony-forming units (CFU )-granulocyte/erythroid/macrophage/megakaryocyte and CFU-granulocyte/macrop hage colonies by CD34(+)CD38(-) enriched progenitors but only in the presen ce of CSF. Additional studies also indicated that AII can act to increase p roliferation in suspension culture. Exposure of CD34(+) cells to AII in sus pension culture, prior to placement in a semisolid medium with erythropoiet in, increased the formation of colonies with more than 50 cells and erythro id progenitors approximately five- and 20-fold, respectively. Further, mRNA for the AT1a receptor was expressed by human bone marrow CD34(+)CD38(-) ce lls, CD34+CD38- cells, and lymphocytes, but not mature myeloid cells. Simil arly, mRNA for the AT1a receptor was expressed on human stromal cell clones , offering further support to the hypothesis that AII arts partially throug h the mesenchymal compartment of the bone marrow. These data suggest that A II may be a factor which stimulates the proliferation of hematopoietic prog enitors.