title: Para-inflammation-mediated retinal recruitment of bone marrow-derived myeloid cells following whole-body irradiation is CCL2 dependent.
abstract: Previous studies have shown that following whole-body irradiation bone marrow (BM)-derived cells can migrate into the central nervous system, including the retina, to give rise to microglia-like cells. The detailed mechanism, however, remains elusive. We show in this study that a single-dose whole-body γ-ray irradiation (8 Gy) induced subclinical damage (i.e., DNA damage) in the neuronal retina, which is accompanied by a low-grade chronic inflammation, para-inflammation, characterized by upregulated expression of chemokines (CCL2, CXCL12, and CX3CL1) and complement components (C4 and CFH), and microglial activation. The upregulation of chemokines CCL2 and CXCL12 and complement C4 lasted for more than 160 days, whereas the expression of CX3CL1 and CFH was upregulated for 2 weeks. Both resident microglia and BM-derived phagocytes displayed mild activation in the neuronal retina following irradiation. When BM cells from CX3CR1(gfp/+) mice or CX3CR1(gfp/gfp) mice were transplanted to wild-type C57BL/6 mice, more than 90% of resident CD11b(+) cells were replaced by donor-derived GFP(+) cells after 6 months. However, when transplanting CX3CR1(gfp/+) BM cells into CCL2-deficient mice, only 20% of retinal CD11b(+) cells were replaced by donor-derived cells at 6 month. Our results suggest that the neuronal retina suffers from a chronic stress following whole-body irradiation, and a para-inflammatory response is initiated, presumably to rectify the insults and maintain homeostasis. The recruitment of BM-derived myeloid cells is a part of the para-inflammatory response and is CCL2 but not CX3CL1 dependent.
authors.affiliation: Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Jiawu
authors.initials: J
authors.lastname: Zhao
authors.forename: Chang
authors.initials: C
authors.lastname: Luo
authors.forename: Sudha Priya Soundara
authors.initials: SP
authors.lastname: Pandi
authors.forename: Rosana G
authors.initials: RG
authors.lastname: Penalva
authors.forename: Denise C
authors.initials: DC
authors.lastname: Fitzgerald
authors.forename: Heping
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D018932:Chemokine CCL2 / Q000502:physiology* / Q000528:radiation effects; D054360:Chemokine CXCL1 / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D018836:Inflammation Mediators