| First Author | Dai M | Year | 2010 |
| Journal | Am J Pathol | Volume | 177 |
| Issue | 6 | Pages | 3089-99 |
| PubMed ID | 21057001 | Mgi Jnum | J:167627 |
| Mgi Id | MGI:4868655 | Doi | 10.2353/ajpath.2010.100340 |
| Citation | Dai M, et al. (2010) Bone marrow cell recruitment mediated by inducible nitric oxide synthase/stromal cell-derived factor-1alpha signaling repairs the acoustically damaged cochlear blood-labyrinth barrier. Am J Pathol 177(6):3089-99 |
| abstractText | Using a mouse model with noise-induced cochlear blood-labyrinth-barrier (CBLB) injury, we examined the effects of inducible nitric oxide synthase (iNOS) on the recruitment of bone marrow-derived cells (BMDCs) to the CBLB after acoustic injury. Lethally irradiated C57BL/6J and B6.129P2-Nos2(tm1Lau)/J mice were transplanted with GFP(+)-BMDCs from C57Bl/6-Tg (UBC GFP) mice. Four weeks after transplantation, we assessed the population of GFP(+)-BMDCs in the CBLB. Only small numbers of GFP(+)-BMDCs were found to infiltrate the area of the CBLB in the control recipient mice. However, robust GFP(+)-BMDC migration occurred in the area of the CBLB within the injured cochlea during the first week following acoustic trauma, and further BMDC accumulation was seen by 2 weeks posttrauma. After 4 weeks, the BMDCs were integrated into vessels. Local iNOS from perivascular resident macrophages was found to be important for BMDC infiltration, since mice deficient in iNOS (Inos(-/-)) and mice with iNOS that had been inhibited by 1400W displayed reduced BMDC infiltration. Stromal cell-derived factor-1alpha (SDF-1alpha) and its chemokine receptor 4 (CXCR4) were required for the iNOS-triggered recruitment. BMDC recruitment was significantly reduced by the inhibition of SDF-1alpha activity. Inhibition of the iNOS/SDF-1alpha signaling pathway reduced vascular repair as observed by reduced vascular density. Our study revealed an intrinsic signaling pathway of iNOS that mediates SDF-1alpha to promote GFP(+)-BMDC infiltration/targeting in cochlear vascular repair. |
