Chemokines and their receptors in allergic disease

Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, South Kensington Campus, Imperial College London, Exhibition Road, London SW7 2AZ.
Journal of Allergy and Clinical Immunology (Impact Factor: 11.48). 09/2006; 118(2):305-18; quiz 319-20. DOI: 10.1016/j.jaci.2006.06.010
Source: PubMed


Mechanisms of chemoattraction underlie the spatial organization of the cells of the immune system under basal conditions and the localization of these cells to sites of inflammation. The chemokines, a family of around 50 small proteins, play a major role in these processes. Leukocytes are equipped with cell-surface sensors for chemokines. There are 19 such receptors that are differentially expressed on leukocytes: the repertoire of receptor expression depending on the type of leukocyte and its stage in maturation. From observations in animal models, clinical studies, in vitro cell biology, and molecular analysis, a working hypothesis has been established to explain the cellular interactions underlying allergic responses and the chemokines-chemokine receptors involved. Chemokines signal through G protein-coupled receptors that are used typically for sensory functions (eg, detection of olfactory signals in the nose). This type of receptor can be blocked selectively by small-molecule antagonists. This provides the opportunity for the development of therapeutic compounds designed to suppress the recruitment of particular leukocyte types in allergic reactions.

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    • "It is expressed mainly on CD9+ eosinophil granulocytes and basophil granulocytes, but also on Th2-cells. CCR3 is known for its role in allergic diseases like allergic asthma, allergic rhinitis, atopic dermatitis and may function by recruiting and activating leukocytes at sites of inflammation [10]. CCR3 is also found on human endothelial cells [8]. "
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    ABSTRACT: Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients with neovascular AMD. Patients with neovascular AMD and healthy controls were included. Blood samples were obtained and prepared for flow cytometry to investigate the expression of CCR3. Levels of CCL11 were measured in plasma using Cytometric Bead Array. Differences between the groups were tested using Kruskal-Wallis test and Mann-Whitney U test. Patients (n = 83) with neovascular AMD and healthy control persons (n = 114) were included in the study. No significant difference in the expression of CCR3 was found on CD9+ granulocytes when comparing patients suffering from neovascular AMD with any of the control groups. We did not find any alteration in CCL11 levels in patients among the age matched groups. There was no correlation between expression of CCR3/CCL11 and clinical response to treatment with anti-vascular endothelial growth factor (VEGF) CONCLUSION: Our results do not suggest a systemic alteration of the CCR3/CCL11 receptor/ligand complex in patients with neovascular AMD.
    Full-text · Article · Feb 2014 · BMC Ophthalmology
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    • "Indeed other chemokines also signal through the CCR3 receptor including CCL5, CCL6, CCL7, CCL8, CCL13 and CCL15, albeit with varying potency. A role for eotaxins in recruitment of cells to sites of allergic inflammation has been well described (Kaplan, 2001; Amerio et al., 2003; Pease and Williams, 2006). However, CCR3 has now been shown to be expressed on cells other than eosinophils, including villous cytotrophoblast , syncytiotrophoblast and EVT (Ishii et al., 2000; Red-Horse et al., 2004; Hanna et al., 2006; Hannan et al., 2006, 2010), suggesting that eotaxins may regulate physiological processes important during placentation . "
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    ABSTRACT: STUDY QUESTION: What are the effects of the eotaxin group of chemokines (CCL11, CCL24 and CCL26) on extravillous trophoblast (EVT) functions important during uterine decidual vessel remodelling? SUMMARY ANSWER: CCL11, CCL24 and CCL26 can regulate EVT migration, invasion and adhesion, highlighting a potential regulatory role for these chemokines during uterine decidual spiral arteriole remodelling in the first trimester of human pregnancy. WHAT IS KNOWN ALREADY: A successful human pregnancy depends on adequate remodelling of the uterine decidual spiral arterioles, a process carried out by EVT which invade from the placenta. The invasion by EVT into the maternal uterine decidual vessels is regulated by the interaction of many factors including members of the chemokine subfamily of cytokines. STUDY DESIGN, SIZE, DURATION: This study used the HTR8/SVneo cell line as a model for invasive EVT. All experiments were repeated on at least three separate occasions. PARTICIPANTS/MATERIALS, SETTING, METHODS: The effect of recombinant human CCL11, CCL24 and CCL26 on EVT migration and invasive potential was measured using the xCELLigence real-time system, wound-healing and Matrigel invasion assays, zymography to measure MMP activity and reverse zymography to measure TIMP activity. A commercially available adhesion assay was used to assess EVT adhesion to extracellular matrix proteins. MAIN RESULTS AND THE ROLE OF CHANCE: All the three eotaxins were found to significantly stimulate migration of the EVT-derived cell line HTR8/SVneo (P < 0.05) with no significant changes in cell number following treatment with each chemokine (P > 0.05). All the three eotaxins significantly increased HTR8/SVneo invasion (P < 0.05) and MMP2 activity (P < 0.05) without any effects on TIMP2 activity (P > 0.05). All the three eotaxins significantly increased HTR8/SVneo cell binding to collagen IV (P < 0.05) and fibronectin (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: This work has been conducted in vitro with a commonly used cell line model of EVT, HTR8/SVneo. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to comprehensively examine the effects of the eotaxin group of chemokines on EVT functions and demonstrates that all the three eotaxins have the ability to regulate EVT functions critical to their role in vessel remodelling. This identifies a new role for the eotaxin group of chemokines during placentation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the Heart Foundation, Australia (G10M 5185). There are no competing interests and the authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
    Full-text · Article · Mar 2013 · Human Reproduction
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    • "Chemokines are secreted basic proteins of 8~10 kDa and are critically important in allergic inflammation via leukocyte trafficking and leukocyte activation. Among them, I- 309 (CCL1), monocyte chemotactic protein-1 (MCP-1/ CCL2), regulated and normal T cell expressed and secreted (RANTES/CCL5), eotaxin(CCL11), MCP-4 (CCL13), thymus and activation regulated chemokine (TARC/CCL17), macrophage inflammatory protein-3α (MIP-3α/CCL20), macrophage-derived chemokine (MDC/CCL22), and cutaneous T-cell-attracting chemokine (CTACK/CCL27) are originated from keratinocytes and may be an effective target for treatment of inflammatory skin diseases (Kaplan, 2001; Pease and Williams, 2006; Luster, 2001). Particularly , an MDC level is closely related with AD and is one of the characteristic features of AD (Kakinuma et al., 2002; Leung et al., 2003; Mantovani et al., 2000). "
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    ABSTRACT: Inflammation is the immune system's response to infection and injury-related disorders, and is related to pro-inflammatory factors (NO, PGE2, cytokines, etc.) produced by inflammatory cells. Atopic dermatitis (AD) is a representative inflammatory skin disease that is characterized by increasing serum levels of inflammatory chemokines, including macrophage-derived chemokine (MDC). Carpinus tschonoskii is a member of the genus Carpinus. We investigated the anti-inflammatory activity of C. tschonoskii by studying the effects of various solvent fractions prepared from its leaves on inflammatory mediators in HaCaT and RAW264.7 cells. We found that the chloroform fraction of C. tschonoskii inhibited MDC at both the protein and mRNA levels in HaCaT cells, acting via the inhibition of STAT1 in the IFN-γ signaling pathway. In addition, the chloroform fraction significantly suppressed the expression of inflammatory factors induced by lipopolysaccharide stimulation, except COX-2 and TNF-α. These results suggest that the chloroform fraction of C. tschonoskii leaves may include a component with potential anti-inflammatory activity.
    Full-text · Article · Dec 2012 · Toxicological Research
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