Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1H-NMR spectroscopy and analytical ultracentrifugation studies reveal that monocyte chemoattractant protein-3 (MCP-3) is a monomer. NMR solution structure shows that MCP-3 adopts an alphabeta fold similar to what is observed in structures of other known chemokines. However, MCP-3 is unique in that it does not show a propensity to form dimers. The closely related chemokines MCP-1 and MCP-2 show a monomer-dimer equilibrium in sedimentation equilibrium studies (approximately 0.2-2 mg/ml). As these proteins are present at nanomolar concentrations in vivo, the results suggest that they are monomeric at functional concentrations and that the monomer is the functionally significant form of MCP-1, MCP-2 and MCP-3.
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PMID:Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3. 889 11

The chemokine receptor CCR5 binds macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated on activation, normal T-cell expressed and secreted (RANTES), and constitutes the major co-receptor allowing infection of CD4(+) T lymphocytes, macrophages, and microglial cells by macrophage-tropic strains of human and simian immunodeficiency virus. CCR5 is most closely related to CCR2b, another chemokine receptor that responds to monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, and MCP-4. We have investigated by mutagenesis the regions of CCR5 and CCR2b involved in the specificity of binding and functional response to their respective ligands. We demonstrate that the key region of CCR5 involved in its specific interaction with MIP-1alpha, MIP-1beta, and RANTES, and its subsequent activation, lies within the second extracellular loop (and possibly the adjacent transmembrane segments). Conversely, the NH2-terminal domain of CCR2b is responsible for the high affinity binding of MCP-1, but is not sufficient to confer activation of the intracellular cascades. Extracellular loops of the receptor, among which the second loop plays a prominent role, are necessary to achieve efficient signaling of the receptor. These data complement our previous mapping of CCR5 domains functionally involved in the fusion process with the human immunodeficiency virus envelope, and will help in the development of agents able to interfere with the early steps of viral infection.
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PMID:The second extracellular loop of CCR5 is the major determinant of ligand specificity. 931 96

A growing family of proteins, known as the chemokines, play an important role in the recruitment and activation of inflammatory cells. The purpose of these studies was to characterize the chemokine receptors present on human sodium butyrate differentiated EoL-3 cells (dEoL-3 cells). Using a combination of 3' rapid amplification of cDNA ends and nested polymerase chain reaction, we detected mRNA for CC chemokine receptor (CCR)1, CCR2, CCR3 and low level of CCR5. Radioligand binding studies demonstrated high-affinity saturable binding for both 125I-macrophage inflammatory protein (MIP)-1alpha and 125I-regulated upon activation normal T cell expressed and secreted (RANTES) with Kd values of 1.4 and 7 nM, respectively. Competition binding with chemokines demonstrated exactly the same rank order of potency for displacement of both ligands: MIP-1alpha approximately monocyte chemoattractant protein (MCP)-3 approximately RANTES > MIP-1beta >> MCP-1 >>> IL-8. RANTES, MCP-3 and MIP-1alpha all produced concentration-dependent transient increases in intracellular calcium concentrations in dEoL-3 cells. Desensitization studies indicated that RANTES, MIP-1alpha and MCP-3 interacted at the same receptor, which is identical in characterization to the cloned CCR1. 125I-MCP-1 also demonstrated high-affinity satuable binding to dEoL-3 cells with a Kd value of 0.4 nM. Competition studies showed that MCP-3 was slightly more potent than MCP-1 and MCP-2. MIP-1alpha, MIP-1beta and RANTES were unable to displace 125I-MCP-1. Addition of either MCP-1 or MCP-3 produced a concentration-dependent elevation of intracellular calcium with a maximun response 2-fold higher than that seen with RANTES or MIP-1alpha. Desensitization studies indicated that MCP-1 and MCP-3 function through CCR2 on these cells. Thus binding and functional studies indicate that dEoL-3 cells express functional CCR1 and CCR2 and that these cells may serve as an important system with which to study the regulation and role of these receptors.
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PMID:Characterization of functional chemokine receptors (CCR1 and CCR2) on EoL-3 cells: a model system to examine the role of chemokines in cell function. 933 50

Human cytomegalovirus (HCMV), a betaherpesvirus, has developed several ways to evade the immune system, notably downregulation of cell surface expression of major histocompatibility complex class I heavy chains. Here we report that HCMV has devised another means to compromise immune surveillance mechanisms. Extracellular accumulation of both constitutively produced monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor-superinduced RANTES (regulated on activation, normal T cell expressed and secreted) was downregulated in HCMV-infected fibroblasts in the absence of transcriptional repression or the expression of polyadenylated RNA for the cellular chemokine receptors CCR-1, CCR-3, and CCR-5. Competitive binding experiments demonstrated that HCMV-infected cells bind RANTES, MCP-1, macrophage inflammatory protein (MIP)-1beta, and MCP-3, but not MCP-2, to the same receptor as does MIP-1alpha, which is not expressed in uninfected cells. HCMV encodes three proteins with homology to CC chemokine receptors: US27, US28, and UL33. Cells infected with HCMV mutants deleted of US28, or both US27 and US28 genes, failed to downregulate extracellular accumulation of either RANTES or MCP-1. In contrast, cells infected with a mutant deleted of US27 continues to bind and downregulate those chemokines. Depletion of chemokines from the culture medium was at least partially due to continuous internalization of extracellular chemokine, since exogenously added, biotinylated RANTES accumulated in HCMV-infected cells. Thus, HCMV can modify the chemokine environment of infected cells through intense sequestering of CC chemokines, mediated principally by expression of the US28-encoded chemokine receptor.
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PMID:Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus-infected cells. 973 Aug 87

Chemokines are a group of inducible, locally acting proinflammatory cytokines which have been implicated in the pathogenesis of a variety of diseases. Important members of the group include monocyte chemoattractant protein (MCP)-1, -2, -3, macrophage inhibitory protein (MIP)-1alpha, -1beta and RANTES (regulated upon activation, normal T expressed and secreted). To facilitate further investigation of the human chemokines, we have constructed a novel multispecific competitor fragment containing primer binding sites for the CC-chemokines MCP-1, MCP-2, MCP-3, MIP-1alpha, MIP-1beta and RANTES, the CXC-chemokines MIP-2alpha, MIP-2beta as well as for the housekeeping gene beta-actin. Using this competitor fragment we can demonstrate reliable semiquantitation of reverse transcribed chemokine mRNAs. The assay should be useful for further studies, in particular for the semiquantitation of chemokine mRNA species from small cell or tissue specimens.
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PMID:Semiquantitation of human chemokine mRNA levels with a newly constructed multispecific competitor fragment. 1035 7

Chemokines mediate their diverse activities through G protein-coupled receptors. The human homolog of the bovine orphan receptor PPR1 shares significant similarity to chemokine receptors. Transfection of this receptor into murine L1.2 cells resulted in responsiveness to monocyte chemoattractant protein (MCP)-4, MCP-2, and MCP-1 in chemotaxis assays. Binding studies with radiolabeled MCP-4 demonstrated a single high affinity binding site with an IC(50) of 0.14 nM. As shown by competition binding, other members of the MCP family also recognized this receptor. MCP-2 was the next most potent ligand, with an IC(50) of 0.45 nM. Surprisingly, eotaxin (IC(50) = 6.7 nM) and MCP-3 (IC(50) = 4.1 nM) bind with greater affinity than MCP-1 (IC(50) = 10.7 nM) but only act as agonists in chemotaxis assays at 100-fold higher concentrations. Because of high affinity binding and functional chemotactic responses, we have termed this receptor CCR11. The gene for CCR11 was localized to human chromosome 3q22, which is distinct from most CC chemokine receptor genes at 3p21. Northern blot hybridization was used to identify CCR11 expression in heart, small intestine, and lung. Thus CCR11 shares functional similarity to CCR2 because it recognizes members of the MCP family, but CCR11 has a distinct expression pattern.
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PMID:CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. 1073 4

We report the cloning of four equine CC chemokines, eotaxin, monocyte chemoattractant protein (MCP)-1, MCP-2 and MCP-4, which show high levels of identity with their respective homologous sequences in other species. Using a multiplex RT-PCR, we have studied the constitutive mRNA expression of these four CC chemokines in skin, lung, liver, spleen, jejunum, colon and kidney of normal adult horses and compared this data with the eosinophil counts in the same samples. We demonstrate that eotaxin mRNA is only expressed in jejunum and colon, where there are large numbers of eosinophils suggesting that eotaxin might be recruiting eosinophils in the normal digestive tract of the horse. MCP-1 and MCP-4 are expressed in all tissues whereas MCP-2 is only found in some samples of lung, spleen, liver and kidney. We also report the early induction (2h) of equine eotaxin and MCP-4, and the up-regulation of MCP-1 by interleukin-4 in dermal fibroblasts, suggesting these chemokines might be involved in equine skin allergic diseases.
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PMID:Cloning of equine chemokines eotaxin, monocyte chemoattractant protein (MCP)-1, MCP-2 and MCP-4, mRNA expression in tissues and induction by IL-4 in dermal fibroblasts. 1104 60

To investigate human basophil responses to chemokines, we have developed a sensitive assay that uses flow cytometry to measure leukocyte shape change as a marker of cell responsiveness. PBMC were isolated from the blood of volunteers. Basophils were identified as a single population of cells that stained positive for IL-3Ralpha (CDw123) and negative for HLA-DR, and their increase in forward scatter (as a result of cell shape change) in response to chemokines was measured. Shape change responses of basophils to chemokines were highly reproducible, with a rank order of potency: monocyte chemoattractant protein (MCP) 4 (peak at <1 nM) >/= eotaxin-2 = eotaxin-3 >/= eotaxin > MCP-1 = MCP-3 > macrophage-inflammatory protein-1alpha > RANTES = MCP-2 = IL-8. The CCR4-selective ligand macrophage-derived chemokine did not elicit a response at concentrations up to 10 nM. Blocking mAbs to CCR2 and CCR3 demonstrated that responses to higher concentrations (>10 nM) of MCP-1 were mediated by CCR3 rather than CCR2, whereas MCP-4 exhibited a biphasic response consistent with sequential activation of CCR3 at lower concentrations and CCR2 at 10 nM MCP-4 and above. In contrast, responses to MCP-3 were blocked only in the presence of both mAbs, but not after pretreatment with either anti-CCR2 or anti-CCR3 mAb alone. These patterns of receptor usage were different from those seen for eosinophils and monocytes. We suggest that cooperation between CCRs might be a mechanism for preferential recruitment of basophils, as occurs in tissue hypersensitivity responses in vivo.
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PMID:Basophil responses to chemokines are regulated by both sequential and cooperative receptor signaling. 1112 Aug 55

CC chemokines are important mediators of immune responses, orchestrating the differential recruitment of various leukocyte populations. Despite the large number of known CC chemokines in other species, no cDNA encoding ovine CC chemokines have been isolated. A homology cloning strategy was utilised to isolate the cDNA of ovine CC chemokines. Full-length monocyte chemoattractant protein (MCP)-1alpha and -2 cDNA have been isolated. The predicted ovine MCP-1alpha amino acid sequence shares 87 and 75% identity with bovine MCP-1alpha and porcine MCP-1, respectively. The predicted ovine MCP-2 amino acid sequence shares 92 and 85% identity with bovine and porcine MCP-2, respectively. Northern blot analysis of MCP-1alpha revealed that it is strongly expressed in cells isolated from mammary lavage fluid (MAL) of ewes given intramammary infusions of Haemonchus contortus. Weak signals were detected in mammary and abomasal tissue. Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products indicates that MCP-1alpha mRNA levels increase in abomasum after challenge with H. contortus. MCP-1alpha mRNA levels were also increased in bronchoalveolar lavage (BAL) cells and lung tissue after house dust mite extract (HDME) challenge. Similarly, MCP-2 mRNA was detected by Northern blot analysis at high levels in MAL cells after H. contortus intramammary infusion, and increased in BAL cells and lung tissue in HDME-challenged sheep. MCP-2 mRNA was not detected by Northern blots in whole mammary or abomasal tissue, but Southern blot analysis of RT-PCR products also indicates that MCP-2 mRNA increases in abomasal tissue after challenge with H. contortus. Hence, two ovine CC chemokine mRNA have been isolated that are up-regulated in response to parasite infection and allergen challenge. Ultimately the isolation of these and other ovine CC chemokines will help elucidate a wide variety of immune responses in sheep.
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PMID:Isolation, characterisation and expression of mRNAs encoding the ovine CC chemokines, monocyte chemoattractant protein (MCP)-1alpha and -2. 1158 31

CC chemokine receptor 5 (CCR5) is a coreceptor for cellular entry of monocyte-tropic (R5) strains of human immunodeficiency virus (HIV) type 1, which has been implicated as the predominant phenotype of HIV in early infection. The CCR5 agonists macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation, normally T cell-expressed and -secreted) have been shown to block replication of R5 virus in vitro and have gained attention as potential antiviral factors. However, a few reports have suggested that other chemokines may also block R5 HIV-1, including monocyte chemoattractant protein (MCP)-2 (CC chemokine ligand 8). We demonstrate that MCP-2 specifically inhibits replication of R5 HIV-1 and that this activity is additive to that of RANTES. Furthermore, MCP-2 induces a robust, pertussis toxin-sensitive calcium flux in primary lymphocytes, and cross-desensitization studies indicate that MCP-2 acts via CCR5. These data confirm that MCP-2 is a ligand for CCR5 on CD4(+) lymphocytes and can specifically block R5 HIV-1.
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PMID:Monocyte chemoattractant protein-2 (CC chemokine ligand 8) inhibits replication of human immunodeficiency virus type 1 via CC chemokine receptor 5. 1193 Mar 29


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