Disease relevance of CX3CR1

• The receptor, now termed CX3CR1, requires pertussis toxin-sensitive G protein signaling to induce migration but not to support adhesion, which also occurs without other adhesion molecules but requires the architecture of a chemokine domain atop the mucin stalk [1].
• Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1 [2].
• CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium [3].
• Expression of fractalkine and its receptor, CX3CR1, in atopic dermatitis: possible contribution to skin inflammation [4].
• Here we describe the distribution of CX3CR1 positive cells in a variety of kidney diseases and renal development [5].
• The intrahepatic mRNA expression of CX3CR1 correlates with the stage of HCV-induced liver fibrosis (P=0.03) [6].

Psychiatry related information on CX3CR1

• CONCLUSIONS: CX3CR1 mediates distinct functional responses in intestinal epithelial cells, which include the autocrine regulation of cell-survival signals and activation of immune modulators, indicating a role of CX3CR1 in host defense mechanisms originating from the intestinal epithelium [7].

High impact information on CX3CR1

• Natural killer cells predominantly express CX3CR1 and respond to fractalkine in both migration and adhesion [1].
• Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion [1].
• Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1 [8].
• Genetic polymorphism in CX3CR1 and risk of HIV disease [9].
• The fractalkine receptor CX3CR1 is a key mediator of atherogenesis [10].

Chemical compound and disease context of CX3CR1

• Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis [11].

Biological context of CX3CR1

• METHODS: CX3CR1 expression in human colonic tissues and intestinal epithelial cell lines was determined by immunohistochemistry, immunoblotting, and reverse-transcription polymerase chain reaction [7].
• Thus, CX3CR1 is expressed by MC and effectively mediates chemotaxis without inducing degranulation [12].
• By reverse transcription-PCR, FK receptor, CX3CR1, is expressed by cultured murine bone marrow-derived MC (BMMC) of both connective tissue and mucosal phenotypes [12].
• Chemokine receptors CX3CR1 and CCR1 were immunolocalized in human first-trimester implantation sites, specifically to endovascular extravillous trophoblasts, but not to the invading interstitial EVTs (iEVTs), with weak staining also on syncytium [13].
• Here two single nucleotide polymorphisms are described in Caucasians in CX3CR1, an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the chemokine fractalkine [8].

Anatomical context of CX3CR1

• Thus, fractalkine and CX3CR1 represent new types of leukocyte trafficking regulators, performing both adhesive and chemotactic functions [1].
• These results demonstrate that FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions [14].
• CX3CR1-mediated activation of intestinal epithelial cells was able to induce migration of human neutrophils into but not through the intestinal epithelial cell monolayer [7].
• Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry [3].
• In contrast, percentages of CD3+/CD8+ memory lymphocytes expressing CX3CR1 were significantly less than percentages of naive CD3+/CD8+ lymphocytes in RA PB, suggesting that this receptor may be down-regulated upon lymphocyte activation [15].

Associations of CX3CR1 with chemical compounds

• Modification of the intervening amino acids between the first two conserved cysteine residues of FKN or vMIP-II indicated a role of the X3 bulge of FKN in affinity and selectivity for CX3CR1 [16].
• CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion [17].
• Fractalkine (CX3CL1), a chemotactic membrane-bound adhesion factor, and its receptor (CX3CR1) were assessed by immunohistochemistry in endometrial samples across the menstrual cycle, in early pregnancy, and in women using progestin-only contraceptives [18].
• Resveratrol may provide a new pharmacological approach for suppressing fractalkine/CX3CR1-mediated injury in inflammatory conditions [19].
• INTRODUCTION: We sought to investigate whether there was a difference between cyclosporine (CsA) and mycophenolate mofetil (MMF) to affect the expression of Fractalkine/CX3CR1 in chronic allograft nephropathy (CAN) [20].

Physical interactions of CX3CR1

• In steady state experiments, all three CX3CR1 isoforms bound CX3CL1 with similar affinity [21].
• METHODS: The mRNA-expression of G protein-coupled CX3CR1 was analyzed by RT-PCR [22].
• RSV G protein contains a CX3C chemokine motif that interacts with the CX3CR1 chemokine receptor and modifies the activities of fractalkine [23].
• Such a study for the first time revealed that as compared to genomic profile within normal blood mononuclear cells, the cells derived from rheumatic heart disease patients exhibited significantly higher expression of genes coding for IL-8, IFN-gamma and CX3CR1 coupled with significant downregulation of CD36 mRNA expression [24].

Regulatory relationships of CX3CR1

• RESULTS: CX3CR1 expression by peripheral CD4+ and CD8+ T cells was up-regulated in RA patients [3].
• There is a positive correlation between the number of fractalkine-expressing cells and the number of CX3CR1-positive cells in human atherosclerotic plaques (r=0.70, n=15 plaques) [25].

Other interactions of CX3CR1

• Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis [3].
• CONCLUSIONS: Chemokines produced by cytokine activated PTEC promote the selective recruitment of activated T cells via the receptors, CCR5, CXCR3 and CX3CR1 [26].
• Chemotaxis of these cells was inhibited by blocking CCR5, CXCR3 and CX3CR1 by 69%, 71% and 29% respectively, with complete inhibition following combined blockade [26].
• These results suggest that the ligand for the putative CMKBRL1 receptor is a beta chemokine that targets both neutrophils and monocytes [27].
• A human cDNA encoding a putative G protein-coupled receptor designated chemokine beta receptor-like 1 (CMKBRL1) was isolated from an eosinophilic leukemia library [27].

Analytical, diagnostic and therapeutic context of CX3CR1

• CMKBRL1 mRNA was detectable by Northern blot hybridization in neutrophils and monocytes, but not eosinophils, and was also found in eight solid organs that were tested with particularly high expression in brain [27].
• In two retrospective studies, CX3CR1 has been implicated in the pathogenesis of atherosclerotic cardiovascular disease (CVD) based on statistical association of a common receptor variant named CX3CR1-M280 with lower prevalence of atherosclerosis, coronary endothelial dysfunction, and acute coronary syndromes [28].
• By RT-PCR, we found enhanced expression of Fkn and CX3CR1 mRNA on day 18 in rat AIA, a time of pronounced inflammation in the rat joint [29].
• CONCLUSIONS: This exploratory study in heart transplantation suggests that the outcomes of EAR and LAR episodes may be influenced by genetic variant interactions such as "CX3CR1 249I*CCR5 No-E" and "CCR5 E*RANTES -403A."[30]
• In addition to genotyping, CX3CR1 mRNA expression was analyzed by quantitative PCR in 9 HCC specimens and in 6 cases in corresponding non-tumorous liver tissues [31].

References