Rare Pulmonary Connective Tissue Type Mast Cells Regulate Lung Endothelial Cell Angiogenesis.

Within the human lung, mast cells typically reside adjacent to the conducting airway and assume a mucosal phenotype (MC). In rare pathologic conditions, connective tissue phenotype mast cells (MCs) can be found in the lung parenchyma. MCs accumulate in the lungs of infants with severe bronchopulmonary dysplasia, a chronic lung disease associated with preterm birth, which is characterized by pulmonary vascular dysmorphia. The human mast cell line (LUVA) was used to model MCs or MCs. The ability of MCs to affect vascular organization during fetal lung development was tested in mouse lung explant cultures. The effect of MCs on in vitro tube formation and barrier function was studied using primary fetal human pulmonary microvascular endothelial cells. The mechanistic role of MC proteases was tested using inhibitors. MCLUVA but not MCLUVA was associated with vascular dysmorphia in lung explants. In vitro, the addition of MCLUVA potentiated fetal human pulmonary microvascular endothelial cell interactions, inhibited tube stability, and disrupted endothelial cell junctions. Protease inhibitors ameliorated the ability of MCLUVA to alter endothelial cell angiogenic activities in vitro and ex vivo. These data indicate that MCs may directly contribute to disrupted angiogenesis in bronchopulmonary dysplasia. A better understanding of factors that regulate mast cell subtype and their different effector functions is essential.