CX3CL1/fractalkine regulates branching and migration of monocyte-derived cells in the mouse olfactory epithelium

Ruitenberg, Marc J.; Vukovic, Jana; Blomster, Linda V.; Hall, Jarrad M.; Filgueira, Luis; McMenamin, Paul G.; Plant, Giles W.

doi:10.1016/j.jneuroim.2008.09.010

Cited by 39 publications

(29 citation statements)

References 41 publications

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“…A subpopulation of these eGFP ϩ cells coexpressed high levels of MHC-II ( Fig. 1B and C; see also Supplemental Movie online), which bears partial resemblance to previous descriptions of DCs in respiratory epithelia [20] and is in agreement with our earlier findings [13]. Lending further evidence to the presence of a putative MHC-II ϩ DC population, novel data from transgenic CD11c-eYFP mice indeed revealed the presence of CD11c ϩ cells within the olfactory neuroepithelium.…”

Section: Normal Distribution Of Monocyte-derived Cells In the Mouse Osupporting

confidence: 91%

“…4B, and data not shown), and a proportion was also positive for MHC class II (Fig. 4C), thus confirming our earlier observations about the immunophenotype of monocyte-derived cells in the mouse olfactory epithelium [13]. At the 8-week time-point, 42.8 Ϯ 2.7% of eGFP ϩ cells coexpressed MHC-II in mice that had their BM reconstituted from Cx 3 cr1 gfp/ϩ donors.…”

Section: Additional Characterization Of the Phenotype Of CX 3 Cr1 Gfpsupporting

confidence: 89%

“…Images were captured on a Leica TCS SP2 multiphoton confocal microscope at the UWA Centre for Microscopy, Characterisation and Analysis (Crawley, Australia). entire length of septal olfactory neuroepithelium at 6 defined anatomical levels along the rostrocaudal axis of the nasal cavity as described previously [13,19]. The length of the septum was recorded by tracing along the basement membrane using ImagePro (Media Cybernetics, Bethesda, MD, USA).…”

Section: Tissue Processing and Immunostainingmentioning

confidence: 99%

“…We have reported recently that the chemokine CX 3 CL1/ fractalkine is produced by OSNs, and its single known receptor, CX 3 CR1, is present on macrophages and putative DCs in the olfactory neuroepithelium [13]. In light of the increasing interest in the role of macrophages in adult epithelial neurogenesis, we have generated BM chimeric mice to investigate first, the turnover rates of monocyte-derived cells in the nasal neuroepithelium and second, the role of CX 3 CR1 in the recruitment process.…”

Section: Introductionmentioning

confidence: 99%

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Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

Vukovic

Blomster

Chinnery

et al. 2010

Journal of Leukocyte Biology

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Macrophages in the olfactory neuroepithelium are thought to play major roles in tissue homeostasis and repair. However, little information is available at present about possible heterogeneity of these monocyte-derived cells, their turnover rates, and the role of chemokine receptors in this process. To start addressing these issues, this study used Cx₃cr1(gfp) mice, in which the gene sequence for eGFP was knocked into the CX₃CR1 gene locus in the mutant allele. Using neuroepithelial whole-mounts from Cx₃cr1(gfp/+) mice, we show that eGFP(+) cells of monocytic origin are distributed in a loose network throughout this tissue and can be subdivided further into two immunophenotypically distinct subsets based on MHC-II glycoprotein expression. BM chimeric mice were created using Cx₃cr1(gfp/+) donors to investigate turnover of macrophages (and other monocyte-derived cells) in the olfactory neuroepithelium. Our data indicate that the monocyte-derived cell population in the olfactory neuroepithelium is actively replenished by circulating monocytes and under the experimental conditions, completely turned over within 6 months. Transplantation of Cx₃cr1(gfp/gfp) (i.e., CX₃CR1-deficient) BM partially impaired the replenishment process and resulted in an overall decline of the total monocyte-derived cell number in the olfactory epithelium. Interestingly, replenishment of the CD68(low)MHC-II(+) subset appeared minimally affected by CX₃CR1 deficiency. Taken together, the established baseline data about heterogeneity of monocyte-derived cells, their replenishment rates, and the role of CX₃CR1 provide a solid basis to further examine the importance of different monocyte subsets for neuroregeneration at this unique frontier with the external environment.

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Section: Normal Distribution Of Monocyte-derived Cells In the Mouse Osupporting

confidence: 91%

Section: Additional Characterization Of the Phenotype Of CX 3 Cr1 Gfpsupporting

confidence: 89%

Section: Tissue Processing and Immunostainingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

Vukovic

Blomster

Chinnery

et al. 2010

Journal of Leukocyte Biology

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“…The rd8 status of Ins2 Akita mice used in previous studies was not reported at the time. 9 Our study tested the hypothesis that deficiency in Cx 3 cr1, known to be involved in the recruitment of myeloid-derived cells in homeostasis and inflammation, 25,26,47,48 would manifest as microglial changes or the development of characteristic diabetic retinopathy changes in the Ins2…”

Section: Discussionmentioning

confidence: 98%

The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse

Kezic

Chen

Rakoczy

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Diabetic retinopathy (DR) is a major cause of visual impairment in developed countries. While DR has been described classically as a microvascular disease, recent evidence suggests that changes to retinal microglia are an early feature of retinopathy. In our study, we assessed changes in microglial distribution and morphology in vivo and ex vivo in a mouse model of non-proliferative DR, and further examined effects of age and the absence of the functional chemokine receptor Cx 3 cr1 on the progression of these changes. METHODS.To isolate the effects of the three variables: diabetic status, age, and role of Cx 3 cr1, the Ins2Akita mouse was crossed with Cx 3 cr1-eGFP reporter mice. Eyes were assessed clinically in vivo at 10, 20, 30, and 46 weeks of age, and the retinal structure and arrangement of GFP þ microglia was examined ex vivo using whole mount immunofluorescence staining and confocal microscopy.RESULTS. Clinical examination of the fundus, vasculature, or GFP þ microglial distribution did not reveal any macroscopic changes related to diabetic status: however, ex vivo microscopic analysis revealed alterations in microglial network organization, and evidence of cell shape changes regarded classically as signs of activation, in Ins2Akita mice from 10 weeks of age. These changes were exacerbated in older diabetic mice whose microglia lacked Cx 3 cr1 (Ins2 Akita Cx 3 cr1 gfp/gfp mice). Diabetic status and Cx 3 cr1 deficiency led to accumulations of Iba-1 þ hyalocytes (vitreal macrophages) and subretinal macrophages.CONCLUSIONS. These data showed that changes to murine retinal microglia occur in response to systemic diabetic status in the absence of overt retinopathy and inflammation. These changes are exaggerated in mice lacking Cx 3 cr1, suggesting fractalkineCx 3 cr1 interactions may have a role in early neuronal changes in preproliferative DR. (Invest Ophthalmol Vis Sci.

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Neurogenesis in the Adult Olfactory Epithelium

Mackay‐Sim

John

Schwob

2015

Handbook of Olfaction and Gustation

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CX3CL1/fractalkine regulates branching and migration of monocyte-derived cells in the mouse olfactory epithelium

Cited by 39 publications

References 41 publications

Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse

Neurogenesis in the Adult Olfactory Epithelium

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CX3CL1/fractalkine regulates branching and migration of monocyte-derived cells in the mouse olfactory epithelium

Cited by 39 publications

References 41 publications

Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

The Effects of Age and Cx3cr1 Deficiency on Retinal Microglia in theIns2AkitaDiabetic Mouse

Neurogenesis in the Adult Olfactory Epithelium

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The Effects of Age and Cx₃cr1 Deficiency on Retinal Microglia in theIns2^AkitaDiabetic Mouse