Repopulation of cochlear macrophages in murine hematopoietic progenitor cell chimeras: the role of CX3CR1.

ABSTRACT

Cochlear macrophages have been shown to accumulate in the murine cochlea following acoustic trauma. This investigation was performed to determine whether cochlear macrophages could be replaced by donor transplantation of bone marrow precursors. Lethally irradiated C57BL/6 mice were transplanted with hematopoietic precursors from CX3CR1(GFP/GFP) fetal mice. CX3CR1(GFP/GFP) mice express green fluorescent protein (GFP) in monocytes and macrophages and possess no functional CX3CR1. Donor monocytes and macrophages can be easily traced in the wild-type recipient with fluorescent microscopy. We studied mice at 2-16 weeks after transplantation to assess repopulation of cochlear macrophages. A separate group of chimeras was exposed to octave band noise (8-16 kHz for 2 hours) 2 weeks after transplantation to evaluate the migration properties of donor hematopoietic precursors. We found that macrophages derived from donor hematopoietic precursors appeared in cochlea 3-4 weeks after transplantation and increased week by week. Noise exposure induced a massive accumulation of leukocytes, particularly in the spiral ligament of the basal turn. There was no difference between CX3CR1(GFP/GFP) donor/wild-type recipient chimeras and the wild-type donor/wild-type recipient chimeras in hearing thresholds, accumulation of cochlear macrophages, or tissue injury after noise exposure. These data indicate that cochlear macrophages are derived from bone marrow precursors and that they are an exchanging and migratory population. Furthermore, CX3CR1 in hematopoietic precursors is not necessary for macrophage migration into cochlea and when deleted in this cell population, the absence of CX3CR1 does not substantially effect the outcomes after noise.