PT  - JOURNAL ARTICLE
AU  - Yunfeng Zhao
AU  - Liang Guo
AU  - Shaoying Li
AU  - Xueling Wu
TI  - Del-1 reduces endotoxin-induced polymorphonuclear leukocytes adhension and mortality
DP  - 2013 Sep 01
TA  - European Respiratory Journal
PG  - 389
VI  - 42
IP  - Suppl 57
4099  - http://erj.ersjournals.com/content/42/Suppl_57/389.short
4100  - http://erj.ersjournals.com/content/42/Suppl_57/389.full
SO  - Eur Respir J2013 Sep 01; 42
AB  - 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.