Rare Pulmonary Connective Tissue Type Mast Cells Regulate Lung Endothelial Cell Angiogenesis
| Autor: | Thomas J. Mariani, Jinjiang Pang, Yuyan Lyu, Jared A. Mereness, Shumin Wang, Yue Ren |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Angiogenesis Neovascularization Physiologic Connective tissue Cell Line Pathology and Forensic Medicine Neovascularization Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Medicine Mast Cells 030212 general & internal medicine Lung Cells Cultured Bronchopulmonary Dysplasia Tube formation business.industry Endothelial Cells Regular Article Mast cell Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Cell culture medicine.symptom business |
| Zdroj: | Am J Pathol |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2020.04.017 |
| Popis: | Within the human lung, mast cells typically reside adjacent to the conducting airway and assume a mucosal phenotype (MC(T)). In rare pathologic conditions, connective tissue phenotype mast cells (MC(TC)s) can be found in the lung parenchyma. MC(TC)s 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 MC(TC)s or MC(T)s. The ability of MC(TC)s to affect vascular organization during fetal lung development was tested in mouse lung explant cultures. The effect of MC(TC)s on in vitro tube formation and barrier function was studied using primary fetal human pulmonary microvascular endothelial cells. The mechanistic role of MC(TC) proteases was tested using inhibitors. MC(TC)LUVA but not MC(T)LUVA was associated with vascular dysmorphia in lung explants. In vitro, the addition of MC(TC)LUVA potentiated fetal human pulmonary microvascular endothelial cell interactions, inhibited tube stability, and disrupted endothelial cell junctions. Protease inhibitors ameliorated the ability of MC(TC)LUVA to alter endothelial cell angiogenic activities in vitro and ex vivo. These data indicate that MC(TC)s 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. |
| Databáze: | OpenAIRE |
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