CD34+ Progenitor to Endothelial Cell Transition in Post-Pneumonectomy Angiogenesis

In many species, pneumonectomy triggers compensatory lung growth that results in an increase not only in lung volume, but also in alveolar number. Whether the associated alveolar angiogenesis involves the contribution of blood-borne progenitor cells is unknown. To identify and characterize blood-borne progenitor cells contributing to lung growth after pneumonectomy in mice, we studied wild-type and wild-type/green fluorescence protein (GFP) parabiotic mice after left pneumonectomy. Within 21 days of pneumonectomy, a 3.2-fold increase occurred in the number of lung endothelial cells. This increase in total endothelial cells was temporally associated with a 7.3-fold increase in the number of CD34(+) endothelial cells. Seventeen percent of the CD34(+) endothelial cells were actively proliferating, compared with only 4.2% of CD34(-) endothelial cells. Using wild-type/GFP parabiotic mice, we demonstrated that 73.4% of CD34(+) cells were derived from the peripheral blood. Furthermore, lectin perfusion studies demonstrated that CD34(+) cells derived from peripheral blood were almost uniformly incorporated into the lung vasculature. Finally, CD34(+) endothelial cells demonstrated a similar profile, but had enhanced transcriptional activity relative to CD34(+) endothelial cells. We conclude that borne CD34(-) endothelial progenitor cells, characterized by active cell division and an amplified transcriptional signature, transition into resident endothelial cells during compensatory lung growth.