Abstract
Vascularization and blood cell circulation are crucial steps during lung development. However, how blood vessels are generated and when lung circulation is initiated is still a matter of debate. A morpho-functional analysis of pulmonary vasculature was done using human lung samples between 31 and 56 days post-fertilization (pf). The immunolocalization and expression of CD31, CD34, FLT-1, KDR and the vascular growth factor (VEGF) were investigated. The results showed that at day 31 pf, a capillary plexus is already installed, and a few primitive erythroblasts were seen for the first time within the lumen of some blood vessels. Around day 45 pf, an increase in the amount of primitive erythroblasts was detected in the parenchyma surrounding the distal segment of the bronchial tree. The expression of FLT-1, KDR, CD31 and CD34 was observed in endothelial cells of the capillary plexus and the VEGF was detected in the endodermal epithelium. Our results support the hypothesis that the initial formation of the capillary plexus around the tip of the growing airway bud occurs by vasculogenesis, probably regulated by VEGF and KDR. We also showed a very early onset of blood circulation, starting from day 34 pf, concomitant with the generation of new lung buds. In addition, the increasing number of primitive erythroblasts from week 6 onward, associated with a change in the shape of the blood vessels, suggests a remodeling process and that the generation of new distal vessels at the tip of the lung bud occurs mainly by a process of angiogenesis.