@article {Zhao389, author = {Yunfeng Zhao and Liang Guo and Shaoying Li and Xueling Wu}, title = {Del-1 reduces endotoxin-induced polymorphonuclear leukocytes adhension and mortality}, volume = {42}, number = {Suppl 57}, elocation-id = {389}, year = {2013}, publisher = {European Respiratory Society}, abstract = {To investigate the role of Del-1 in PMN adhension in acute lung injury. Human pulmonary micro-vascular endothelium cells (HPMECs) was cocultured with polymorphonuclear leukocytes (PMNs) on HTS Transwell filter plates, then were pre-incubated in presence or absence of recombinant retroviral vector expressing human Del-1 (Retro-hDel-1) or Retro-V(free of any transgenes) before being stimulated with TNF-a (0.732 g ml-1) for 24 hrs. And mice were challenged by intra-peritoneal injection of LPS (15 mg/kg) 48h after gene transfer by Retro-hDel-1 or Retro-v for survival for 7 days. In vitro studies showed the adhension of PMNs with endothelial cells were significantly inhibited and endothelial permeability were dramaticlly decreased in Retro-Del-1 group HPEMCs compared with that of control cells after TNF-a stimulation. The adhension was partially inhibited by LFA-1 pathway through the RGD locus of Del-1 confirmed by site-specific mutagenesis. In vivo studies showed that Del-1 messenger RNA and protein concentration in lung were significantly increased after retrovirus-mediated gene delivery. The lung injury score were significantly decreased in Retro-Del-1 group mice compared with Retro-V group mice after LPS injection at 6 hrs, 24 hrs and 48 hrs. In addition Administration of Retro-hDel-1 significantly improved the survival of mice, relative to a control retrovirus.Up-regulation expression of Retro-hDel-1 restored the integrity of micro-vascular and also altered lung edema induced by LPS through the inhibition of adhesion of PMNs with endothelial cells.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/42/Suppl_57/389}, eprint = {https://erj.ersjournals.com/content/42/Suppl_57/389.full.pdf}, journal = {European Respiratory Journal} }