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

Bicyclams are a novel class of antiviral compounds that are highly potent and selective inhibitors of the replication of HIV-1 and HIV-2. Surprisingly, however, when the prototype compound AMD3100 was tested against M-tropic virus strains such as BaL, ADA, JR-CSF, and SF-162 in human peripheral blood mononuclear cells, the compound was completely inactive. Because of the specific and potent inhibitory effect of AMD3100 on T-tropic viruses, but not M-tropic viruses, it was verified that AMD3100 interacts with the CXC-chemokine receptor CXCR4, the main coreceptor used by T-tropic viruses. AMD3100 dose dependently inhibited the binding of a specific CXCR4 monoclonal antibody to SUP-T1 cells as measured by flow cytometry. It did not inhibit the binding of the biotinylated CC-chemokine macrophage inflammatory protein (MIP) 1alpha or MIP-1beta, ligands for the chemokine receptor CCR5 (the main coreceptor for M-tropic viruses). In addition, AMD3100 completely blocked (a) the Ca2+ flux at 100 ng/ml in lymphocytic SUP-T1 and monocytic THP-1 cells, and (b) the chemotactic responses of THP-1 cells induced by stromal cell-derived factor 1alpha, the natural ligand for CXCR4. Finally, AMD3100 had no effect on the Ca2+ flux induced by the CC-chemokines MIP-1alpha, regulated on activation normal T cell expressed and secreted (RANTES; also a ligand for CCR5), or monocyte chemoattractant protein 3 (a ligand for CCR1 and CCR2b), nor was it able to induce Ca2+ fluxes by itself. The bicyclams are, to our knowledge, the first low molecular weight anti-HIV agents shown to act as potent and selective CXCR4 antagonists.
 ...
PMID:Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. 933 78

Recent data suggest that mast cells (MC) are involved in the regulation of leukocyte accumulation in inflammatory reactions. In this study, expression of leukocyte-chemotactic peptides (chemokines) in purified human lung MC (n = 16) and a human mast cell line, HMC-1, was analyzed. Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) showed baseline expression of monocyte chemoattractant protein (MCP)-1 mRNA in unstimulated MC. Exposure of MC to recombinant stem cell factor (rhSCF, 100 ng/mL) or anti-IgE (10 microgram/mL) was followed by a substantial increase in expression of MCP-1 mRNA. Neither unstimulated nor stem cell factor (SCF )-stimulated lung MC expressed transcripts for interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, or RANTES by Northern blotting. The mast cell line HMC-1, which contains a mutated and intrinsically activated SCF-receptor, was found to express high levels of MCP-1 mRNA in a constitutive manner. Exposure of HMC-1 cells to rhSCF resulted in upregulation of MCP-1 mRNA expression, and de novo expression of MIP-1beta mRNA. The SCF-induced upregulation of MCP-1 mRNA in lung MC and HMC-1 was accompanied by an increase in immunologically detectable MCP-1 in cell supernatants (sup) (lung MC [<98%], control medium, 1 hour: 159 +/- 27 v SCF, 100 ng/mL, 1 hour: 398 +/- 46 pg/mL/10(6) cells; HMC-1: control, 1 hour: 894 +/- 116 v SCF, 1 hour: 1,536 +/- 265 pg/mL/10(6)). IgE-dependent activation was also followed by MCP-1 release from MC. MC-sup and HMC-1-sup induced chemotaxis in blood monocytes (Mo) (control: 100% +/- 12% v 2-hour-MC-sup: 463% +/- 38% v HMC-1-sup: 532% +/- 12%), and a monoclonal antibody (MoAb) to MCP-1 (but not MoAb to IL-8) inhibited Mo-chemotaxis induced by MC-sup or HMC-1-sup (39% to 55% inhibition, P < .05). In summary, our study identifies MCP-1 as the predominant CC-chemokine produced and released in human lung MC. MCP-1 may be a crucial mediator in inflammatory reactions associated with MC activation and accumulation of MCP-1-responsive leukocytes.
 ...
PMID:The c-kit ligand stem cell factor and anti-IgE promote expression of monocyte chemoattractant protein-1 in human lung mast cells. 937 54

T effector subsets, such as Th1 or Th2 cells, are key players in inflammatory reactions. It is not known whether chemokines are able to recruit these subsets differentially, as has been shown for memory vs naive T cells. Here we demonstrate that Th1 and Th2 cells differ in their intrinsic migratory properties and their chemotactic responsiveness toward distinct chemokines. While the CC-chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES were efficient chemoattractants for Th1 cells, inducing a dose-dependent transmigration, Th2 cells were not attracted by these chemokines. Another CC-chemokine, JE/monocyte chemoattractant protein (MCP)-1, and a CXC-chemokine, stromal cell-derived factor (SDF)-1alpha, exerted chemotactic effects on both Th1 and Th2 cells, but differences in sensitivity and the percentage of responding cells were recorded between both subsets. These results indicate that chemokines play a distinct role in the regulation of local immune reactions by influencing the local balance between proinflammatory and antiinflammatory T cell subsets.
 ...
PMID:T helper 1 and T helper 2 cells respond differentially to chemokines. 955 86

Hepatic ischemia reperfusion injury as well as acute graft rejection (RE) after orthotopic liver transplantation (OLT) are associated with leukocyte invasion of the graft. Local synthesis of chemokines is a key reaction in the recruitment and activation of inflammatory leukocytes and consequent liver damage. In this paper we describe the role of monocyte chemoattractant protein (MCP)-1 (CCL2) in human OLT. We investigated the serum CC-chemokine levels for MCP-1 by specific ELISAs after OLT in 105 human liver allografts between September 1997 and January 2001. One hour after reperfusion we saw a significant (t test) increase of MCP-1 in peripheral blood (92.5 +/- 85.8 pg/mL to 774.2 +/- 319.6 pg/mL, 8.3-fold, P <.0001), hepatic venous blood (92.5 +/- 85.8 pg/mL to 866.7 +/- 376.1 pg/mL, 9.3-fold, P <.0001), and portal venous blood (92.5 +/- 85.8 pg/mL to 792.9 +/- 408.0 pg/mL, 8.5-fold, P < 0.0001) during hepatic ischemia reperfusion injury. An analysis of the correlation (Spearman's test, rs) between the expression of MCP-1 and the AST (rs 0.555, P <.025) and ALT (rs 0.852, P <.0001) showed a significant linear correlation. During RE a significant (t test) increase of MCP-1 (125.5 +/- 95.6 pg/mL to 188.5 +/- 124.6 pg/mL, 3.86-fold, P <.0001) was demonstrated. The successful treatment of the RE led again to a decline to lower base levels. Hepatic ischemia reperfusion syndrome as well as RE after OLT are characterized by typical patterns of CCL-2 overexpression. This finding proposes a new noninvasive, early diagnostic test after OLT.
 ...
PMID:The role of monocyte chemoattractant protein-1 in orthotopic liver transplantation. 1282 89

CC-chemokine ligand 2 (CCL2/monocyte chemoattractant protein 1) is known to have an important role on T helper type 2 (Th2) cell generation and described to induce interleukin (IL)-4 production by activated T cells. In the present study, an increase of CCL2 production in cultures of peripheral blood lymphocytes (PBL) from patients with severe thermal injuries was demonstrated. Severe combined immunodeficiency (SCID) mice reconstituted with PBL from healthy donors (PBL-SCID chimeras) were resistant to infection with herpes simplex virus type 1 (HSV-1). Treatment of these chimeras with recombinant human CCL2 resulted in an increased susceptibility to the same HSV-1 infection. However, human SCID mouse chimeras created by PBL depleted of natural killer T (NKT) cells (NKT(-) PBL-SCID chimeras) were resistant to HSV-1 infection, even though they were treated with CCL2. IL-4 was not detected in the sera of NKT(-) PBL-SCID chimeras treated with CCL2, while IL-4 was detected in the sera of PBL-SCID chimeras under the same CCL2 administration. NKT cells isolated from PBL were shown to be cells not responsible for CCL2-stimulated IL-4 production. However, in the presence of CCL2, IL-4 was detected in culture fluids of NKT cells co-cultured with naive T cells. This cytokine was produced in co-cultures of NKT cells pretreated with CCL2 (CCL2-NKT cells) and naive T cells. In addition, IL-4 production was demonstrated in transwell cultures of CCL2-NKT cells and naive T cells. These results suggest that NKT cells lacking IL-4 producing abilities contribute to the CCL2-associated increase in the susceptibility of thermally injured patients to HSV-1 infection through the induction of Th2 cell generation.
 ...
PMID:Role of natural killer T (NKT) cells lacking interleukin (IL)-4 producing abilities on the CC-chemokine ligand 2-associated herpes simplex virus type 1 infection in human severe combined immunodeficiency (SCID) mouse chimeras. 1568 84

CC-chemokine-encoding DNA vaccine has been reported to be capable of inducing immunologic memory to corresponding pathogenic self CC-chemokines in animal models of autoimmune disease. This study investigated whether introduction of a foreign T helper epitope into monocyte chemoattractant protein 1 (CCL2) DNA vaccine could boost its immunogenicity by inducing strong neutralizing autoantibody against the pathogenic chemokine CCL2 sufficiently to be protective in a classically nonimmune model of disease, Adriamycin nephropathy (AN). Modification of the CCL2 DNA vaccine by replacing a surface loop region of CCL2 sequence with tetanus toxoid T helper epitope P30 elicited a strong self-specific CCL2 autoantibody production, as well as an IFN-gamma-producing T cell cellular response. The increased immunogenicity of modified CCL2 DNA vaccination but not unmodified CCL2 DNA vaccination was protective against functional and structural renal injury in rat AN. The protective effect of the modified CCL2 DNA vaccine was associated with blockade of glomerular and interstitial macrophage recruitment by neutralizing autoantibody against CCL2, which plays a critical role in eliciting renal injury in AN. Therefore, modification with a foreign T helper epitope breaks self-tolerance by inducing a cellular and humoral response against self-protein and provides a strategy to increase the potency of DNA vaccination sufficiently to afford protection in toxin-induced chronic renal disease.
 ...
PMID:DNA vaccination with CCL2 DNA modified by the addition of an adjuvant epitope protects against "nonimmune" toxic renal injury. 1639 66

Severe stress decreases the resistance of hosts exposed to microbial infections. As compared with two groups of control mice (normal mice, food-and-water-deprived mice [FWD mice]), restraint-stressed mice (RST mice) were shown to be greatly susceptible to intracerebral growth of Cryptococcus neoformans. The susceptibility of FWD mice to cerebral cryptococcosis increased to the level shown in RST mice, when these groups of mice were inoculated with microglial cells from the brains of RST mice. However, the susceptibility of FWD mice to cerebral cryptococcosis was not influenced by the adoptive transfer of microglial cells from normal mice or FWD mice. Microglial cells from RST mice produced CC-chemokine ligand-2 (CCL-2/monocyte chemoattractant protein 1), but not microglial cells from FWD mice. The resistance of RST mice to cerebral cryptococcosis was improved to the extent shown in FWD mice, when they were treated with anti-CCL-2 antibody. However, the susceptibility of normal mice and FWD mice to cerebral cryptococcosis increased to that shown in RST mice, when they were treated with rCCL-2. Microglial cells from RST mice were discriminated from the same cell preparations derived from FWD mice by their abilities to produce CCL-2, to phagocytize C. neoformans cells and to express Toll-like receptor 2. These results indicate that the resistance of RST mice to cerebral cryptococcosis is diminished by CCL-2 produced by microglial cells that are influenced by restraint stress.
 ...
PMID:Microglial cells from psychologically stressed mice as an accelerator of cerebral cryptococcosis. 1695 90