Para-inflammation-mediated retinal recruitment of bone marrow-derived myeloid cells following whole-body irradiation is CCL2 dependent

Mei Chen, Jiawu Zhao, Chang Luo, Sudha Priya Soundara Pandi, Rosana G. Penalva, Denise C. Fitzgerald, Heping Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

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 ?-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 CX3CR1gfp/+ mice or CX3CR1gfp/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 CX3CR1gfp/+ 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.
Original languageEnglish
Pages (from-to)833-842
Number of pages10
JournalGlia
Volume60
Issue number5
Early online date23 Feb 2012
DOIs
Publication statusPublished - May 2012

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

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