| First Author | Burton VJ | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 1 | Pages | 333-41 |
| PubMed ID | 20724539 | Mgi Jnum | J:168440 |
| Mgi Id | MGI:4888202 | Doi | 10.1182/blood-2010-05-285973 |
| Citation | Burton VJ, et al. (2011) Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function. Blood 117(1):333-41 |
| abstractText | Mutations in bone morphogenetic protein receptor II (BMPR-II) underlie most heritable cases of pulmonary arterial hypertension (PAH). However, less than half the individuals who harbor mutations develop the disease. Interestingly, heterozygous null BMPR-II mice fail to develop PAH unless an additional inflammatory insult is applied, suggesting that BMPR-II plays a fundamental role in dampening inflammatory signals in the pulmonary vasculature. Using static- and flow-based in vitro systems, we demonstrate that BMPR-II maintains the barrier function of the pulmonary artery endothelial monolayer suppressing leukocyte transmigration. Similar findings were also observed in vivo using a murine model with loss of endothelial BMPR-II expression. In vitro, the enhanced transmigration of leukocytes after tumor necrosis factor alpha or transforming growth factor beta1 stimulation was CXCR2 dependent. Our data define how loss of BMPR-II in the endothelial layer of the pulmonary vasculature could lead to a heightened susceptibility to inflammation by promoting the extravasation of leukocytes into the pulmonary artery wall. We speculate that this may be a key mechanism involved in the initiation of the disease in heritable PAH that results from defects in BMPR-II expression. |
