Molecular Cloning and Functional Expression of a Novel CC Chemokine Receptor cDNA from a Human Basophilic Cell Line

Power, Christine; Meyer, Angela; Nemeth, Karin; Bacon, Kevin B.; Hoogewerf, Arlene J.; Proudfoot, Amanda E. I.; Wells, Timothy N.C.

doi:10.1074/jbc.270.33.19495

Cited by 238 publications

(172 citation statements)

References 43 publications

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“…CCR4 binds CCL2, -3, -5, -17 and -22 [26,28]. However, other reports have shown that CCL17 and -22, but not CCL2, -3 and -5 are specific functional ligands for CCR4 [29][30][31].…”

Section: Discussionmentioning

confidence: 92%

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Migration of cytotoxic T lymphocytes toward melanoma cells in three‐dimensional organotypic culture is dependent on CCL2 and CCR4

et al. 2006

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Studies in experimental animal models have demonstrated that chemokines produced by tumor cells attract chemokine receptor-positive T lymphocytes into the tumor area. However, in cancer patients, the role of chemokines in T lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the migration of a melanoma patient's CTL toward autologous tumor cells has been studied in a novel three-dimensional organotypic melanoma culture. In this model, CTL migrated toward tumor cells, resulting in tumor cell apoptosis. CTL migration was mediated by the CC chemokine receptor (CCR)4 expressed by the CTL and the CC chemokine ligand (CCL)2 secreted by the tumor cells, as evidenced by blockage of CTL migration by CCL2 or antibodies to CCL2 or CCR4. These results were confirmed in a Transwell migration assay in which the CTL actively migrated toward isolated CCL2 and migration was inhibited by anti-CCR4 antibody. These studies, together with previous studies in mice indicating regression of CCL2-transduced tumor cells, suggest that CCL2 may be useful as an immunotherapeutic agent for cancer patients.

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“…CCR4 binds CCL2, -3, -5, -17 and -22 [26,28]. However, other reports have shown that CCL17 and -22, but not CCL2, -3 and -5 are specific functional ligands for CCR4 [29][30][31].…”

Section: Discussionmentioning

confidence: 92%

“…CCR4, a seven-transmembrane G-protein-coupled receptor, is expressed on monocytes, T cells, B cells, basophils, NK cells, immature DC and adult T cell leukemia [26][27][28]. CCR4 binds CCL2, -3, -5, -17 and -22 [26,28].…”

Section: Discussionmentioning

confidence: 99%

Migration of cytotoxic T lymphocytes toward melanoma cells in three‐dimensional organotypic culture is dependent on CCL2 and CCR4

et al. 2006

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“…Macrophage-derived chemoattractant (also termed as CCL22) exerts its chemokine effect by binding to its receptor CCR4 (also termed as CD194 and K5-5), a type of G protein-coupled receptor found on Th2 cells, monocytes, and various other cell types. 27,28 T-cell infiltration has been implicated in response to central nervous system injury and it has been suggested that a systemic Th2 shift may improve outcome. 29 This would imply that MDC might play a part in a healing process.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Interleukin-1 Receptor Antagonist in Severe Traumatic Brain Injury: A Phase II Randomized Control Trial

Helmy

Guilfoyle

Carpenter

et al. 2014

J Cereb Blood Flow Metab

144

169

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Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rhIL1ra-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time.

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“…Subsequently, a second CC chemokine receptor, CC CKR-2, was identified as being a high affinity receptor for MCP-1 [8]. Recently two new RANTES/MIP<z receptors have been cloned: CC CKR-3 which is expressed in eosinophils [9] and CC CKR-4 from a basophilic cell line, KU812 [10].…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the RANTES/MIP‐1α receptor (CC CKR‐1) stably transfected in HEK 293 cells and the recombinant ligands

Proudfoot¹,

Power²,

Hoogewerf³

et al. 1995

FEBS Letters

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The CC chemokines RANTES and MIP-I~ are known to activate certain leucocytes and leucocytie cell lines. We have produced and fully cbaracterised the recombinant proteins expressed in E. coil They induce ehemotaxis of the pro-monoc)tic cell line, THP-1 and T cells. THP-1 cells express three of the known CC chemokine receptors. In order to study the activation of a single receptor, we have expressed the shared receptor ((C CKR-1) for RANTES and MIP-la stably in the HEK 293 cell line. We have examined the effects of RANTES and MIP-la on the CC CKR-1 transfectants by equilibrium binding studies and in a ebemotaxis assay. RANTES competes for pZSlIRAN-TES with an ICs0 of 0.6 + 0.23 nM, whereas MIP-la competes for its radiolabelled counterpart with an ICs0 of 10 + 1.6 nM in the transfeetants. These affinities are the same as those measured on the THP-1 call line. The stably transfected HEK 293 cells respond to both these chemokines in the chemotaxis assay with the same ECso values as those measured for THP-1 cells. This indicates that this cellular response can be mediated through the CC CKR-1 receptor.

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Molecular Cloning and Functional Expression of a Novel CC Chemokine Receptor cDNA from a Human Basophilic Cell Line

Cited by 238 publications

References 43 publications

Migration of cytotoxic T lymphocytes toward melanoma cells in three‐dimensional organotypic culture is dependent on CCL2 and CCR4

Migration of cytotoxic T lymphocytes toward melanoma cells in three‐dimensional organotypic culture is dependent on CCL2 and CCR4

Recombinant Human Interleukin-1 Receptor Antagonist in Severe Traumatic Brain Injury: A Phase II Randomized Control Trial

Characterisation of the RANTES/MIP‐1α receptor (CC CKR‐1) stably transfected in HEK 293 cells and the recombinant ligands

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