Monocyte differentiation in the ischemic lung

Angiogenesis after pulmonary ischemia is initiated by reactive O 2 species (Nijmeh, 2010), is dependent on chemokine growth factors, and extent of neovascularization is correlated with the number of lavaged macrophages. Blood monocytes differentiate into lung parenchymal monocytes/macrophages (CD11B+, CD11C+/−) and alveolar macrophages (CD11B−CD11C+). In this study, we questioned whether macrophage subpopulations were differentially expressed and which subset contributed to growth factor release. We characterized CD11B+ low and CD11C+ surface markers (flow cytometry) in left lungs from mice 24 hrs after left pulmonary artery ligation (LPAL; n=5 experiments/time point). In left lung homogenates, all CD11B+/C+ cells increased 24 h after LPAL (vs 0 h). No changes in proliferation were seen in any subset (PCNA; 0 h vs 24 h lungs). When CD11C+ and CD11B+ macrophages were harvested separately from naïve lungs (microbead extraction, n=6 experiments), the secreted chemokine MIP‐2 (ELISA) increased after exposure to H 2 O 2 (46%), hyaluronan fragments (70%) and both stimuli (93%) only in CD11C+ macrophages and remained unchanged in CD11B+ cells. These data suggest that oxidative stress within the ischemic lung contributes to the differentiation of immature monocytes to mature macrophages and induces release of a growth factor previously shown to be essential for neovascularization. Supported by: HL071605