title: Lesion response of long-term and recently immigrated resident endoneurial macrophages in peripheral nerve explant cultures from bone marrow chimeric mice.
abstract: Resident macrophages of the peripheral nervous system have recently been shown to respond rapidly to Wallerian degeneration before the influx of blood-derived macrophages. Because resident endoneurial macrophages are slowly but incompletely exchanged from the blood within 3 months, they could potentially comprise a heterogenous cell population consisting of long-term resident cells and more mobile cells undergoing turnover. We used bone marrow chimeric mice created by transplanting bone marrow from green fluorescent protein-transgenic mice into irradiated wildtype recipients to selectively analyse the response of these two resident macrophage populations to Wallerian degeneration in sciatic nerve explant cultures. In such nerves, recently immigrated macrophages exhibit green fluorescence whereas long-term resident macrophages do not. Studies in cultures from wildtype controls revealed rapid morphological changes of resident macrophages towards a bloated phenotype, a proliferative response resulting in a 3.7-fold increase of macrophage numbers over 2 weeks, and phagocytosis of myelin basic protein-immunoreactive myelin debris. When chimeric mice were analysed, both populations of resident endoneurial macrophages participated in morphological transformation, proliferation and phagocytosis. Quantitative studies revealed a stronger proliferative and phagocytic response in long-term resident endoneurial macrophages compared with recently immigrated macrophages. Our results point towards subtle, but not principal, differences between the two macrophage populations, which might indicate different stages of macrophage differentiation rather than the existence of entirely distinct endoneurial macrophage populations. The results further underline the versatility of resident endoneurial macrophages following peripheral nerve injury, which is reminiscent of the lesion response of microglial cells within the brain.
authors.affiliation: Department of Neurology, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, D-48129 Münster, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Leonhard
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.forename: William F
authors.initials: WF
authors.lastname: Hickey
authors.forename: Erich B
authors.initials: EB
authors.lastname: Ringelstein
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kiefer
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D000949:Histocompatibility Antigens Class II; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010525:Peripheral Nerves / Q000473:pathology; D010587:Phagocytosis; D012584:Sciatic Nerve / Q000473:pathology; D013997:Time Factors; D018183:Transplantation Chimera; D014855:Wallerian Degeneration / Q000473:pathology*
chemical_list: D000949:Histocompatibility Antigens Class II