Bone marrow cell recruitment mediated by inducible nitric oxide synthase/stromal cell-derived factor-1α signaling repairs the acoustically damaged cochlear blood-labyrinth barrier

Min Dai, Yue Yang, Irina Omelchenko, Alfred L. Nuttall, Allan Kachelmeier, Ruijuan Xiu, Xiaorui Shi

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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-1α (SDF-1α) and its chemokine receptor 4 (CXCR4) were required for the iNOS-triggered recruitment. BMDC recruitment was significantly reduced by the inhibition of SDF-1α activity. Inhibition of the iNOS/SDF-1α signaling pathway reduced vascular repair as observed by reduced vascular density. Our study revealed an intrinsic signaling pathway of iNOS that mediates SDF-1α to promote GFP+-BMDC infiltration/targeting in cochlear vascular repair.

Original languageEnglish (US)
Pages (from-to)3089-3099
Number of pages11
JournalAmerican Journal of Pathology
Volume177
Issue number6
DOIs
StatePublished - Dec 2010

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Bone marrow cell recruitment mediated by inducible nitric oxide synthase/stromal cell-derived factor-1α signaling repairs the acoustically damaged cochlear blood-labyrinth barrier'. Together they form a unique fingerprint.

  • Cite this