Hypertensive Stimuli Increase Pro-Inflammatory Bone Marrow Derived Macrophages In Vitro

Renal macrophage infiltration and inflammation is a hallmark of hypertension (HTN). An imbalance in macrophages has been observed in murine salt-sensitive and angiotensin II (AngII)-induced models of HTN. We have identified increased activated macrophages (CD45+ CD11b+ F4/80+ CD38+), pro-inflammatory M1 macrophages (CD45+ CD11b+ F4/80+ CD11c+ CD206-), and activated M1 macrophage (CD45+ CD11b+ F4/80+ CD11c+ CD206- CD38+) in the kidneys of these mice. In this study, we hypothesized that salt and AngII directly induce macrophages to become activated and pro-inflammatory. We exposed bone marrow derived macrophages (BMDMs) grown in GM-CSF to salt (190 μm) and AngII (0.01 μm) and found that there were significant increases in renal activated macrophages (% of CD45 cells: Con: 31 ± 1; AngII: 37 ± 1; Salt: 56 ± 1), pro-inflammatory M1 macrophages (Con: 27 ± 1; AngII: 37 ± 1; Salt: 56 ± 1), and activated M1 macrophages (Con: 22 ± 1; AngII: 28 ± 1; Salt: 43 ± 1) as determined by flow cytometry. However, the cultivation of BMDMs in M-CSF, the more traditional growth factor present in culturing BMDMs, did not produce the same significant results. Next, we will identify renal pro-inflammatory cytokines, chemokines, growth factors, and levels of GM-CSF present in these mouse models of HTN. Currently, these findings suggest that GM-CSF increases macrophage responsiveness to HTN stimuli and induces activated and pro-inflammatory macrophages which may contribute to the development and progression of HTN. Targeting activated renal macrophages or renal GM-CSF may provide a new therapeutic option for the treatment of HTN.