Bone marrow-derived elements in the peripheral nervous system: An immunohistochemical and ultrastructural investigation in chimeric rats

BACKGROUND: Currently available studies on the peripheral nervous system (PNS) give little information on the presence, distribution, turnover and function of bone marrow-derived cells such as monocytes, macrophages, and dendritic cells. To address such issues, the present investigation of PNS tissues from bone marrow transplanted chimeras was performed. EXPERIMENTAL DESIGN: Inbred DA rats were lethally irradiated and transplanted with (Lewis x DA)F₁ bone marrow carrying the non-DA major histocompatibility antigens from Lewis rats. The anti-RT-1A₁ antibody (anti-Lewis MHC class I), I1-69, and the macrophage markers, Ed2 and Ox42 were used to visualize immunohistochemically donor bone marrow-derived cells and resident macrophages of sensory and autonomic ganglia as well as in peripheral nerves. RESULTS: In the ganglia, up to 80% and within peripheral nerves, up to 60% of macrophages were replaced by donor cells within 3 months of established chimerism. Ultrastructurally these cells were located: (a) between the perineurial sheaths, (b) in a perivascular position, or (c) freely dispersed within the endoneurium but outside the basal lamina of Schwann cells and ganglion cells. On the rare occasions where myelin and axonal pathology was noted, or during central chromatolysis of ganglion cells, donor marrow- derived cells became positioned under the basal lamina and incorporated tissue debris. CONCLUSIONS: These data suggest a rapid and significant turnover of bone marrow-derived cells within the PNS. Our observations are relevant to the understanding of the pathogenesis of reactive, immunologic, and HIV-associated processes within the PNS.