Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine

Raychaudhuri, S. P.; Jiang, Wanling; Farber, Eugene M.

doi:10.1046/j.1365-2133.2001.04219.x

Cited by 55 publications

(36 citation statements)

References 29 publications

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“…Multiple reparative processes were affected by the receptor, including inflammation, fibrosis, neovascularization, and regeneration of parenchymal cells. The results are consistent with previous reports showing that the CX3CL1-CX3CR1 ligand-receptor pair plays an important role in the initiation and progression of inflammation (12)(13)(14), and is up-regulated in inflammatory diseases (20 -23, 26, 27, 42), including inflammatory diseases of the skin (15,16,19). Our data linking CX3CR1 to fibrosis in skin wound healing are consistent with a report of CX3CL1 and CX3CR1 expression in the skin and lung of patients with systemic sclerosis (16), and an in vivo study showing that CX3CR1 KO mice have reduced collagen accumulation and renal fibrosis in a model of ischemia-reperfusion injury (18).…”

Section: Discussionsupporting

confidence: 82%

Chemokine Receptor CX3CR1 Mediates Skin Wound Healing by Promoting Macrophage and Fibroblast Accumulation and Function

Ishida

Gao

Murphy

2008

The Journal of Immunology

278

243

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Wounds heal through a highly regulated, self-limited inflammatory response, however, precise inflammatory mediators have not been fully delineated. In this study, we report that in a mouse model of excisional skin wound healing the chemokine CX3CL1 and its receptor CX3CR1 were both highly induced at wound sites; CX3CL1 colocalized with macrophages and endothelial cells, whereas CX3CR1 colocalized mainly with macrophages and fibroblasts. Loss of CX3CR1 function delayed wound closure in both CX3CR1 knockout (KO) mice and in wild-type mice infused with anti-CX3CR1-neutralizing Ab. Conversely, transfer of bone marrow from donor wild-type mice, but not from donor CX3CR1 KO mice, restored wound healing to normal in CX3CR1 KO-recipient mice. Direct effects of CX3CR1 disruption at the wound site included marked reduction of macrophages and macrophage products, such as TGF-β1 and vascular endothelial growth factor. Consistent with this, we observed reduced α-smooth muscle actin (a marker for myofibroblasts) and collagen deposition in skin from wounded CX3CR1 KO mice, as well as reduced neovascularization. Together, the data support a molecular model of skin wound repair in which CX3CR1 mediates direct recruitment of bone marrow-derived monocytes/macrophages which release profibrotic and angiogenic mediators.

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Section: Discussionsupporting

confidence: 82%

Chemokine Receptor CX3CR1 Mediates Skin Wound Healing by Promoting Macrophage and Fibroblast Accumulation and Function

Ishida

Gao

Murphy

2008

The Journal of Immunology

278

243

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“…Since expression of FKN and expression of CX3CR1 can be induced by immune cells, studies have focused on the role of FKN as an inflammatory mediator. Indeed, FKN is up-regulated in the inflammatory site of rheumatoid arthritis (12,18), inflammatory bowel disease (19), atherosclerosis (20), psoriasis (21), myositis (22), and various inflammatory conditions of the kidney (23) and brain (24), although FKN gene-disrupted mice did not show significant differences from wild-type mice in either steady-state or inflammatory conditions (25).…”

Section: F Ractalkine (Cx3cl1 Fknmentioning

confidence: 99%

Dose-Dependent Differential Regulation of Cytokine Secretion from Macrophages by Fractalkine

Mizutani

Sakurai

Shibata

et al. 2007

The Journal of Immunology

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Although expression of the fractalkine (CX3CL1, FKN) is enhanced in inflamed tissues, it is detected at steady state in various organs such as the intestine, and its receptor CX3CR1 is highly expressed in resident-type dendritic cells and macrophages. We hypothesized that FKN might regulate the inflammatory responses of these cells. Therefore, murine macrophages were pretreated with FKN and then stimulated with LPS. We found that macrophages pretreated with 0.03 nM FKN but not with 3 nM FKN secreted 50% less TNF-α than did cells treated with LPS alone. Cells treated with 0.03 nM FKN and LPS also showed reduced phosphorylation of ERK1/2 and reduced NF-κB p50 subunit. Interestingly, the p65 subunit of NF-κB was translocated to the nuclei but redistributed to the cytoplasm in the early phase by forming a complex with peroxisome proliferator-activated receptor (PPAR) γ. Exogenous 15-deoxy-Δ(12,14)-prostaglandin J2, a natural ligand for PPAR-γ, also induced redistribution of p65 with decreased TNF-α secretion after LPS challenge. Pretreatment with 0.03 nM but not 3 nM FKN increased the cellular levels of 15-deoxy-Δ(12,14)-prostaglandin J2 as well as mRNA of PPAR-γ. Requirement of PPAR-γ for the effect of 0.03 nM FKN was confirmed by small interfering RNA of PPAR-γ. In contrast, pretreatment with 3 nM FKN induced higher levels of IL-23 compared with cells pretreated with 0.03 nM FKN and produced TNF-α in a CX3CR1-dependent manner. These dose-dependent differential effects of FKN establish its novel role in immune homeostasis and inflammation.

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“…17 It is involved in many skin inflammatory diseases 18 such as psoriasis, eczema and atopic dermatitis, and is associated with the terminal cutaneous nerve [nerve growth factor (NGF) receptor positive]. 19 Using our model and various activity tests, we demonstrated that chemokine action is endothelial cell origin-selective. On the one hand, CCL21 and CX3CL1 specifically induced a T4 activated cell line (CEMT4) lymphocyte adhesion on human peripheral lymph node endothelial cells, clone B3 (HPLNEC.B3), and human appendix endothelial cells (HAPEC), respectively, whereas CXCL12 and CCL5 did not display any specific action.…”

Section: Introductionmentioning

confidence: 99%

Selective human endothelial cell activation by chemokines as a guide to cell homing

et al. 2009

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SummaryAn original model of organo-specific, immortalized and stabilized endothelial cell lines was used to delineate the part played by some chemokines (CCL21, CX3CL1, CCL5 and CXCL12) and their receptors in endothelium organo-specificity. Chemokine receptor expression and chemokine presentation were investigated on organo-specific human endothelial cell lines. Although the chemokines showed distinct binding patterns for the various endothelial cell lines, these were not correlated with the expression of the corresponding receptors (CX3CR1, CXCR4, CCR5 and CCR7). Experiments with CCL21 on peripheral lymph node endothelial cells demonstrated that the chemokine did not co-localize with its receptor but was associated with extracellular matrix components. The specific activity of chemokines was clearly shown to be related to the endothelial cell origin. Indeed, CX3CL1 and CCL21 promoted lymphocyte recruitment by endothelial cells from the appendix and peripheral lymph nodes, respectively, while CX3CL1 pro-angiogenic activity was restricted to endothelial cells from the appendix and skin. The high specificity of the chemokine/endothelium interaction allowed the design of a direct in vitro endothelial cell targeting assay. This unique cellular model demonstrated a fundamental role for chemokines in conferring on the endothelium its organo-specificity and its potential for tissue targeting through the selective binding, presentation and activation properties of chemokines.

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Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine

Cited by 55 publications

References 29 publications

Chemokine Receptor CX3CR1 Mediates Skin Wound Healing by Promoting Macrophage and Fibroblast Accumulation and Function

Chemokine Receptor CX3CR1 Mediates Skin Wound Healing by Promoting Macrophage and Fibroblast Accumulation and Function

Dose-Dependent Differential Regulation of Cytokine Secretion from Macrophages by Fractalkine

Selective human endothelial cell activation by chemokines as a guide to cell homing

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