CD11b interstitial macrophages are required for ischemia-induced lung angiogenesis.

The importance of myeloid cells in promoting neovascularization has been shown in a number of pathological settings in several organs. However, the specific role of macrophages in promoting systemic angiogenesis during pulmonary ischemia is not fully determined. Our past work suggested that cells of monocytic lineage contributed to systemic angiogenesis in the lung since clodronate-induced depletion of all macrophages resulted in attenuated neovascularization. Our current goals were to define the population of macrophages important for systemic vessel growth into the lung after the onset of pulmonary ischemia in mice. Interstitial macrophages (CD64 MerTK CD11b ) increased significantly as did the percent of CD45 Ly6G neutrophils 1 day after the induction of left lung ischemia, despite the fact there was limited cell recruitment due to complete obstruction of the left pulmonary artery in this ischemia model. Since both interstitial macrophages and neutrophils express CD11b, we used CD11b DTR mice and showed the critical role for these cells since CD11b depleted mice showed no systemic angiogenesis 7 days after the onset of ischemia when compared to control mice. Coculture of mouse aortic endothelial cells with macrophages showed increased proliferation relative to endothelial cells in culture without inflammatory cells, or pulmonary artery endothelial cells. We conclude that CD11b leukocytes, trapped within the lung at the onset of ischemia, contribute to growth factor release, and are critical for new blood vessel proliferation.