TY - JOUR T1 - Enhanced expression of Robo4 ameliorates LPS-induced acute lung injury in mice JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p2042 AU - Xueling Wu AU - Yuanlin Song AU - Xiaodan Zhu AU - Xiaocong Fang AU - Chunxue Bai Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p2042.abstract N2 - The loss of endothelial integrity which causes leak of fluid and proteins into tissues contributes to the disease and death associated with acute lung injury. Slit2/Robo4 (an endothelium-specific) signaling promotes vascular stability. The purpose of this study was to evaluate the effect of enhanced expression of Robo4 on LPS-induced acute lung injury. We constructed a recombinant adenoviral vector expressing murine Robo4 (Ad.mRobo4) which were administered intranasally to BALB/c mice. Forty-eight hours later, all the mice were administered a single dose of LPS via i.p. injection to induce acute lung injury. A second cohort of mice was followed for survival for 7 days. Administration of Ad.m Robo4 increased increased the expression of Robo4 in lung tissue, as determined by reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry. Enhanced expression of Robo4 in lung suppressed the inflammatory reaction to LPS, attenuated the lung pathological changes, significantly reduced vascular permeability and edema in the lung determined by albumin in bronchoalveolar lavage fluid and also improved the survival of mice. Our results demonstrate a novel function manner for slit2/Robo4 signaling. Slit2/Robo4 pathway work formerly mainly considered as ligand-dependently, it has now to be considered as a ligand-independently and thus could be an attractive adjuvant in the treatment of acute lung injury. ER -