title: Perivascular macrophage-like melanocyte responsiveness to acoustic trauma--a salient feature of strial barrier associated hearing loss.
abstract: Tissue perivascular resident macrophages (PVM/Ms), a hybrid cell type with characteristics of both macrophages and melanocytes, are critical for establishing and maintaining the endocochlear potential (EP) required for hearing. The PVM/Ms modulate expression of tight- and adherens-junction proteins in the endothelial barrier of the stria vascularis (intrastrial fluid-blood barrier) through secretion of a signaling molecule, pigment epithelium growth factor (PEDF). Here, we identify a significant link between abnormalities in PVM/Ms and endothelial barrier breakdown from acoustic trauma to the mouse ear. We find that acoustic trauma causes activation of PVM/Ms and physical detachment from capillary walls. Concurrent with the detachment, we find loosened tight junctions between endothelial cells and decreased production of tight- and adherens-junction protein, resulting in leakage of serum proteins from the damaged barrier. A key factor in the intrastrial fluid-blood barrier hyperpermeability exhibited in the mice is down-regulation of PVM/M modulated PEDF production. We demonstrate that delivery of PEDF to the damaged ear ameliorates hearing loss by restoring intrastrial fluid-blood barrier integrity. PEDF up-regulates expression of tight junction-associated proteins (ZO-1 and VE-cadherin) and PVM/M stabilizing neural cell adhesion molecule (NCAM-120). These studies point to the critical role PVM/Ms play in regulating intrastrial fluid-blood barrier integrity in healthy and noise-damaged ears.
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology/Head and Neck Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Lingling
authors.initials: L
authors.lastname: Neng
authors.forename: Jin Hui
authors.initials: JH
authors.lastname: Zhang
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Zhi
authors.forename: Anders
authors.initials: A
authors.lastname: Fridberger
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Shi
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D004423:Ear / Q000293:injuries / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D034381:Hearing Loss / Q000378:metabolism* / Q000473:pathology*; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology
keywords: acoustic trauma; endothelial cell; instrastrial fluid-blood barrier; mouse cochlea; paracellular permeability