Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of six synthetic CC chemokines, MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human blood monocytes were studied. All CC chemokines elicited a bimodal migration response in vitro. Highest numbers of migrating cells were obtained with the monocyte chemotactic proteins (MCP) and RANTES, somewhat lower numbers with MIP-1 alpha, and only weak migration with MIP-1 beta. The most potent attractants were MCP-1 and MIP-1 alpha which reached maximum efficacy at 0.1 to 1 nM. All CC chemokines also induced the release of N-acetyl-beta-D-glucosaminidase from cytochalasin B-pretreated monocytes. The MCP were most effective (MCP-1 > MCP-3 > MCP-2), RANTES and MIP-1 alpha showed moderate (1/3 of MCP-1 activity), and MIP-1 beta only minimal activity. Cytosolic free Ca2+ changes and exocytosis were used to monitor receptor desensitization. Marked cross-desensitization was observed among MCP-1, MCP-2 and MCP-3 on the one hand, and RANTES, MIP-1 alpha and MIP-1 beta on the other, indicating receptor sharing within these two subgroups of CC chemokines. The responses to RANTES, MIP-1 alpha and MIP-1 beta were also moderately to markedly desensitized by pretreatment with MCP-1, MCP-2 or MCP-3, while the responses to the MCP were virtually unaffected by pretreatment with RANTES, MIP-1 alpha and MIP-1 beta. These results suggest that the MCP also interact with receptors recognized by RANTES, MIP-1 alpha and MIP-1 beta, but not vice versa. Binding studies were performed with radiolabeled MCP-1 or MIP-1 alpha. All MCP competed readily for labeled MCP-1 yielding a concentration-dependent sigmoidal displacement curve. Displacement with RANTES, MIP-1 alpha and MIP-1 beta was observed at higher concentrations, but was not complete. Radiolabeled MIP-1 alpha was displaced efficiently by MIP-1 alpha or MIP-1 beta, but only partially by RANTES. Of the MCP, only MC-3 completely displaced MIP-1 alpha, while only partial displacement was observed with MCP-1 and MCP-2.
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PMID:Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human monocytes. 753 Nov 49

Trafficking to tissues and then to lymph nodes is a crucial aspect of the immunobiology of dendritic cells. The present study was designed to identify molecules able to direct the migration of human blood-derived dendritic cells. fMLP (representative of formyl peptides of bacterial origin), C5a, and the C-C chemokines monocyte chemotactic protein (MCP)-3, MIP-1 alpha/LD78, and RANTES elicited chemotactic migration and a rise of intracellular free calcium in dendritic cells. In contrast, the C-X-C chemokines IL-8 and IP-10 and the C-C chemokines MCP-1 and MCP-2 were inactive as chemoattractants. Thus, dendritic cells respond to classical chemotactic signals and to a set of chemokines distinct from that active on monocytes and neutrophils. Chemoattractants are likely to contribute to localization and trafficking of dendritic cells and provide tools to recruit these cells in the design of immunization strategies.
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PMID:Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. 756 Oct 21

Chemoattractants, including chemokines such as interleukin 8 (IL-8) and related proteins, activate leucocytes via seven-transmembrane-domain G-protein-coupled receptors. A cDNA for a novel receptor of this kind consisting of 327 amino acids was isolated from a human blood monocyte cDNA library. The polypeptide, termed monocyte-derived receptor 15 (MDR15), is an alternative form of the Burkitt's lymphoma receptor 1 (BLR1) encoded by a human Burkitt's lymphoma cDNA [Dobner, Wolf, Emrich and Lipp (1992) Eur. J. Immunol. 22, 2795-2799]. MDR15 and BLR1 cDNAs differ in the 5' region, where the open reading frame of MDR15 is shorter by 45 codons. Southern-blot analysis indicates that the two transcripts for MDR15 and BLR1 are encoded by the same gene. Northern-blot analysis using a probe that hybridizes with both mRNAs demonstrated high-level expression in chronic B-lymphoid leukaemia and non-Hodgkin's lymphoma cells and, to a lesser extent, peripheral blood monocytes and lymphocytes. Reverse transcription-PCR studies with MDR15- and BLR1-specific primers showed similar levels of transcripts for both receptors in RNA that was positive in Northern-blot analysis. MDR15 and BLR1 have high structural similarity to receptors for human IL-8 (about 40% amino acid identity) and other chemokines. However, none of a series of radiolabelled chemokines (IL-8, NAP-2, GRO alpha, PF4, IP10, MCP-1, MCP-2, MCP-3, I-309, RANTES and MIP-1 alpha) and other ligands (C3a and leukotriene B4) bound to Jurkat transfectants that stably expressed either MDR15 or BLR1 mRNA. The fact that MDR15 and BLR1 are expressed on leucocytes and show marked sequence similarity to chemokine receptors suggests the existence of as yet unidentified chemokines. Alternative transcript formation affecting the 5'-terminal part of the coding region may be a way to modify ligand-binding selectivity.
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PMID:Sequence variation of a novel heptahelical leucocyte receptor through alternative transcript formation. 763 92

Two subfamilies of chemokines are distinguished depending on the arrangement of the first two of four conserved cysteines, which are either separated by one amino acid (CXC chemokines) or adjacent (CC chemokines). IL-8 and the other CXC chemokines act preferentially on neutrophils, while the CC chemokines (MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta) act on monocytes, but not neutrophils, and have additional activities toward basophil and eosinophil granulocytes, and T-lymphocytes. Several chemokine receptors have been identified, all of which belong to the seven-transmembrane-domain type and are coupled to G-proteins. The discovery of chemokines has provided the basis for the understanding of leukocyte recruitment and activation in inflammation and other disturbances of tissue homeostasis.
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PMID:Interleukin-8 and the chemokine family. 765 3

The responses of lymphocytes to six CC chemokines--MCP-1, MCP-2, MCP-3, MIP-1 alpha, MIP-1 beta, and RANTES--were studied using cloned human CD4+ and CD8+ T cells. All CC chemokines tested induced migration of both types of lymphocytes, whereas two CXC chemokines used as controls, IL-8 and IP-10, were inactive. The monocyte chemotactic proteins (MCP-1, MCP-2, and MCP-3) showed a typically bimodal concentration dependence, and were considerably more effective than MIP-1 alpha, MIP-1 beta, or RANTES. All CC chemokines also induced a rapid and transient rise in cytosolic free Ca2+ in either type of T cell. The rise was prevented by Bordetella pertussis toxin treatment, indicating that G-protein-coupled receptors are involved in signaling. It was most pronounced with MCP-1 and MCP-3, which is in agreement with the efficacy of these chemokines as chemoattractants. The responses to MCP-2, MIP-1 alpha, MIP-1 beta, and RANTES were weaker, and no changes were obtained on stimulation with IL-8 or IP-10. Freshly isolated human blood lymphocytes were also tested, but neither migration nor Ca2+ changes were observed. Low numbers of high-affinity receptors for MCP-1 were found on CD4+ and CD8+ cells ( < 900 per cell, Kd < 1 nM), and desensitization experiments showed that MCP-1, MCP-2, and MCP-3 share receptors. Owing to their superior effectiveness on CD4+ and CD8+ T cells, the monocyte chemotactic proteins could play a major role in the recruitment of activated T lymphocytes.
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PMID:Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes. 792 71

Chemokines are a superfamily of structurally related cytokines involved in leukocyte recruitment in normal and neoplastic tissues. The availability of non-cross-reacting reagents specific for each member of the C-C and C-X-C family is important for careful characterization of their in vitro and in vivo production and relevance. Here we describe a novel, highly specific, mAb against monocyte chemotactic protein-1 (MCP-1). The 5D3-F7 mAb (IgG1,kappa) recognizes human recombinant and natural MCP-1 in ELISA, immunoprecipitation and immunoblot analysis. As a source of natural MCP-1 we used the 8387 human sarcoma line which produces spontaneously MCP-1 and responds to TNF with increased expression and release. The 5D3-F7 mAb inhibited the chemotactic activity of MCP-1 for monocytes. Using the 5D3-F7 mAb and a polyclonal rabbit anti-MCP-1 serum, a sandwich ELISA was developed. In both the direct and the sandwich ELISA, the 5D3-F7 mAb recognized human MCP-1, but not the closely related C-C chemokines MCP-1, MCP-2, MCP-3, MIP-1 alpha, and RANTES and the C-X-C chemokines IL-8, gro alpha and NAP-2. In culture supernatants the sensitivity of the sandwich ELISA was approximately equal to 30 pg/ml. The sandwich ELISA permitted detection of MCP-1 in resting or cytokine-stimulated endothelial, mesothelial and Kaposi's sarcoma cells. Preliminary immunohistochemical analysis revealed production of MCP-1 by macrophage-like cells at sites of inflammation. The 5D3-F7 mAb provides a novel, highly specific reagent with which to investigate the in vitro and in vivo production and role of MCP-1.
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PMID:A new monoclonal antibody (5D3-F7) which recognizes human monocyte-chemotactic protein-1 but not related chemokines. Development of a sandwich ELISA and in situ detection of producing cells. 808 29

Several chemotactic agonists including interleukin-8 (IL-8) and related cytokines have been shown to activate and attract leukocytes via seven-transmembrane domain, GTP-binding protein-coupled receptors. A cDNA clone, LESTR, encoding a protein of 352 amino acids, corresponding to a novel receptor of this type, was isolated from a human blood monocyte cDNA library. The sequence of the deduced protein, LESTR (leukocyte-derived seven-transmembrane domain receptor), has 92.6% identity with that of a recently reported bovine neuropeptide Y (NPY) receptor, boLCR1 (Rimland, J., Xin, W., Sweetnam, P., Saijoh, K., Nestler, E. J., and Duman, R. S. (1991) Mol. Pharmacol. 40, 869-875). LESTR, however, is more similar (> 34%) to the IL-8 receptors, IL-8R1 and IL-8R2, than to several NPY receptors of different origin (< 20%). In the monocyte library, LESTR cDNA fragments were about 20 times as frequent as cDNA coding for IL-8R1 and IL-8R2, and much higher levels of LESTR- than IL-8R-specific mRNA were found in human blood neutrophils and lymphocytes. LESTR transcripts, by contrast, were low or undetectable in several neuroblastoma cell lines that are widely used to study NPY functions. Transfected cells expressing high levels of LESTR mRNA did not bind radiolabeled NPY, IL-8, NAP-2, GRO alpha, PF4, IP10, MCP-1, MCP-3, MIP-1 alpha, HC14, I309, RANTES, C3a, or LTB4. NPY also failed to bind to neutrophils, monocytes, and lymphocytes, to elicit responses in vitro such as Ca2+ changes, shape change, chemotaxis, enzyme release, and the respiratory burst, and to induce leukocyte accumulation upon injection in rats and rabbits. Although the ligand for LESTR could not be identified among a large number of chemotactic cytokines, the high expression in white blood cells and the marked sequence relation to IL-8R1 and IL-8R2 suggest that LESTR may function in the activation of inflammatory cells.
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PMID:Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. 827 99

The beta subfamily of chemokines contains cytokine-like factors which are chemotactic for human basophils and eosinophils. The also stimulate these cells to secrete pro-inflammatory substances such as histamine or eosinophil cationic protein. MCAF/MCP-1, MCP-2, MCP-3, RANTES and MIP-1 alpha all attract and stimulate basophils; MCP-1 and MCP-3 are the most potent. RANTES, MCP-3 and to a lesser degree MIP-I alpha are chemotactic factors and activators of eosinophils. Cytokines such as IL3, IL5 and GM CSF can augment the responses of these cells to the various chemokines and function as primers. These substances may have particular importance as mediators of allergic inflammation, particularly the late phase component of the response.
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PMID:Chemokines and the allergic response. 852 99

The responses of cloned human NK cells (ERNK57) to seven CC chemokines (monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and 1309) and two CXC chemokines (IL-8 and IP-10) were studied. Except for 1309, all CC chemokines induced chemotaxis of the NK cells in vitro, whereas the CXC chemokines were inactive. Maximal activity was obtained at 1 nM for MCP-1 and 10 to 100 nM for the other CC chemokines. The response showed a typically bimodal concentration dependence in all cases, except for RANTES, which induced a linear increase of migration over the concentration range of 0.1 to 1000 nM. A transient rise of the cytosolic-free Ca2+ concentration ([Ca2+]i), which is characteristic for chemokine-stimulated leukocytes, was observed in NK cells after stimulation with all six active chemokines. Since granule exocytosis is required for NK cell-dependent target killing, the effect of CC chemokines on exocytosis was tested. All CC chemokines that induced chemotaxis and [Ca2+]i changes also induced the release of granzyme A and N-acetyl-beta-D-glucosaminidase from cloned and blood NK cells, as well as CD8+ T cells after pretreatment with cytochalasin B. Maximum release was obtained from NK cells, and amounted to 35% and 13% of the total content of granzyme A and N-acetyl-beta-D-glucosaminidase, respectively. The capacity of cloned NK cells and CD8+ T cells to respond to chemokines depended on the time in culture after stimulation with PHA in the presence of irradiated feeder cells, and maximum responses were observed after 10 to 16 days. Our results demonstrate that CC chemokines activate NK cells, and are, therefore, not only attractants for monocytes, T lymphocytes, and eosinophil and basophil granulocytes.
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PMID:Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release. 859 80

The cloning of several receptors activated by either CC or CXC chemokines and belonging to the G protein-coupled family of receptors has been reported recently. In the present work, we describe the cloning of a human gene, named ChemR13, encoding a new CC-chemokine receptor. The gene encodes a protein of 352 amino acids with a calculated molecular mass of 40 600 Da and displaying a single potential site for N-linked glycosylation. Using a set of overlapping lambda clones, the genomic organisation of the locus was investigated, demonstrating that the ChemR13 gene is physically linked, and in the same orientation, as the CC-CKR2 gene that encodes a receptor for the monocyte chemoattractant protein-1 (MCP-1). A distance of 17.5 kb separates the two coding regions, which share 75% identity in nucleic acid and amino acid sequences. Human ChemR13 was functionally expressed in a stably transfected CHO-K1 cell line. Physiological responses to chemokines were monitored using a microphysiometer. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) was the most potent agonist. MIP-1 beta and RANTES were also active at physiological concentrations. The other CC-chemokines, MCP-1, MCP-2 and MCP-3, as well as CXC-chemokines (IL-8, GRO alpha) had no effect. ChemR13 receptor transcripts were detected by Northern blotting in the promyeloblastic cell line KG-1A, suggesting a potential role in the control of granulocytic lineage proliferation or differentiation. ChemR13 is thus a new member of the growing family of chemokine receptors that mediate the recruitment of cells involved in immune and inflammatory processes. Being the fifth functionally identified receptor in his class, this new CC-chemokine receptor (CC-CKR) is tentatively designated CC-CKR5.
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PMID:Molecular cloning and functional expression of a new human CC-chemokine receptor gene. 863 85


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