title: Temporal changes in monocyte and macrophage subsets and microglial macrophages following spinal cord injury in the Lys-Egfp-ki mouse model.
abstract: The role of hematogenous (hMΦ) and microglial (mMΦ) macrophages following spinal cord injury (SCI) remains unclear as they are not distinguished easily from each other in the lesion area. We have recently described the temporal and spatial response to SCI of each MΦ population using the lys-EGFP-ki mouse that enables EGFP(+) hMΦ to be distinguished from EGFP(-) mMΦ at the lesion site. In the present study, we characterized the response of monocyte and hMΦ subsets and mMΦ to SCI. We describe, for the first time, the responses of circulating classical (pro-inflammatory) and non-classical monocyte subsets to SCI. Additionally, we show the presence of classical and non-classical hMΦ at the SCI lesion. Importantly, we demonstrate that the 'classical pro-inflammatory' hMΦ respond in the acute (1d, 3d) stages of SCI while the 'non-classical' hMΦ respond in the sub-acute (7d, 14d) phase of SCI. At later time points (6weeks post injury) classical hMΦ return to the injury site. Our study offers new insight into the cellular inflammatory response that occurs after SCI and suggests that the timing and targets of anti-inflammatory therapies may be crucial to maximize neuroprotection at the acute and more chronic stages of SCI.
authors.affiliation: BioTherapeutics Research Laboratories and Spinal Cord Injury Team, Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada, N6A 5K8.
authors.forename: Sakina G
authors.initials: SG
authors.lastname: Thawer
authors.forename: Leah
authors.initials: L
authors.lastname: Mawhinney
authors.forename: Kristin
authors.initials: K
authors.lastname: Chadwick
authors.forename: Sonali N
authors.initials: SN
authors.lastname: de Chickera
authors.forename: Lynne C
authors.initials: LC
authors.lastname: Weaver
authors.forename: Arthur
authors.initials: A
authors.lastname: Brown
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Dekaban
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D049452:Green Fluorescent Proteins; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000145:classification / Q000276:immunology* / Q000473:pathology; D009000:Monocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D009113:Muramidase; D013119:Spinal Cord Injuries / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D013997:Time Factors
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D009113:Muramidase; C472450:lysozyme M, mouse
keywords: Classical inflammatory monocytes; Lys-EGFP-ki mouse; M1/M2 macrophage polarization; Non-classical monocytes