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Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines are a family of low-molecular-weight proinflammatory cytokines that stimulate recruitment of leukocytes. The chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) are relatively specific chemoattractants for neutrophils and monocytes, respectively. Chemokine expression contributes to the presence of different leukocyte populations observed in normal and pathologic states. In the present studies, peripheral blood mononuclear cells (PBMC) were stimulated by microbes (Candida albicans, Streptococcus mutans, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) selected based upon their importance as oral pathogens. IL-8 and MCP-1 gene expression and protein release were determined by Northern blot (RNA blot) analysis and enzyme-linked immunosorbent assay. C. albicans, P. gingivalis, and A. actinomycetemcomitans induced high levels of production of both MCP-1 and IL-8. S. mutans was a strong inducer of MCP-1, but it did not stimulate significant production of IL-8. C. albicans, S. mutans, and A. actinomycetemcomitans were 500 to 5,000 times more potent than P. gingivalis in terms of MCP-1 production. In general, the microbe-to-PBMC ratios required for maximum gene expression of MCP-1 were lower than those for IL-8. However, for actual protein release of MCP-1 versus IL-8, differences in the effects of various microbe concentrations were observed only for A. actinomycetemcomitans. These results demonstrate that different oral pathogens induce specific dose-dependent patterns of chemokine gene expression and release. Such patterns may help explain the immunopathology of oral infections, particularly with regard to inflammatory leukocyte recruitment.
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PMID:Monocyte chemoattractant protein 1 and interleukin-8 production in mononuclear cells stimulated by oral microorganisms. 889 Jan 91

The chemokines are a large family of cytokines that regulate the complex and precise recruitment of immune cells into inflammatory foci. To fully appreciate their role in the pathogenesis of human diseases, the entire spectrum of chemokines, their receptors, their cellular targets, and mechanisms of regulation need to be delineated. Using eotaxin as a probe, we isolated a cDNA for a novel human beta (or CC) chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-4. Purified recombinant MCP-4 protein was a potent chemoattractant for monocytes and eosinophils and stimulated histamine release from basophils. MCP-4 induced a calcium flux in HEK-293 cells transfected with the monocyte selective MCP-1 receptor (CCR-2B) and the eosinophil selective eotaxin receptor (CCR-3), but not in the more widely expressed CCR-1 or CCR-5. This novel chemokine is expressed in TNF-alpha and IL-1 activated epithelial and endothelial cells in vitro, and in the epithelial mucosa of patients with both Th2-type allergic and Th1-type nonallergic sinusitis. Furthermore, both IFN-gamma and IL-4, products of Th1 and Th2 cells, respectively, synergized with TNF-alpha and IL-1 in inducing MCP-4 mRNA accumulation. These properties of MCP-4 offer a molecular explanation for the observed accumulation of monocytes, eosinophils and basophils in both Th1- and Th2-type immune responses.
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PMID:Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3. 895 14

The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was up-regulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.
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PMID:Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1. 899 46

The chemokine monocyte chemoattractant protein 1 (MCP-1) is produced predominantly by mononuclear phagocytes and stimulates recruitment into infected tissues of blood monocytes and T cells. These cell types are thought to be critical to host defenses against infections due to Cryptococcus neoformans, a major cause of disease in persons with AIDS and other disorders of cell-mediated immunity. Accordingly, in the present study, we examined the conditions under which human monocytes and bronchoalveolar macrophages (BAM) are stimulated by C. neoformans to produce MCP-1. C. neoformans was a potent inducer of MCP-1 release from monocytes, with levels of chemokine secreted similar to that seen following stimulation with lipopolysaccharide (LPS). BAM, in contrast, were stimulated by LPS, but not by C. neoformans, to secrete MCP-1. A peak in MCP-1 mRNA was seen 8 h following cryptococcal stimulation of monocytes. Nine strains of C. neoformans stimulated monocytes to release MCP-1, and there was only modest variation between strains. However, when an individual strain was used, the capacity of C. neoformans to stimulate monocyte MCP-1 release did vary, depending upon the conditions used to grow the fungal stimuli. Finally, C. neoformans stimulated comparable quantities of MCP-1 release in monocytes from donors with and without human immunodeficiency virus infection. These data establish C. neoformans as a potent stimulator of MCP-1 in monocytes, but not in BAM. The failure of C. neoformans to stimulate MCP-1 in BAM, if occurring in vivo, could result in a diminished cell-mediated inflammatory response following inhalation of airborne fungi.
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PMID:Variables affecting production of monocyte chemotactic factor 1 from human leukocytes stimulated with Cryptococcus neoformans. 903 95

The bone-cement interface tissue of failed total hip arthroplasty (THA) has inflammatory characteristics, such as the presence of prostaglandin E2 and interleukin 1 (IL-1). We considered that the bone-cement interface tissue could be the site of granulomatous inflammation caused by a foreign-body reaction. It has been demonstrated that inflammatory cytokines and chemokines have an important role in granulomatous inflammation. Bone-cement interface tissue was obtained at revision from nine patients with failed cemented THA, and the role of macrophages was assessed by immunohistochemistry, electron microscopy, and molecular biological techniques. We used the reverse-transcriptional polymerase chain reaction to examine the expression of mRNA for IL-1 alpha, IL-1 beta, tumor necrosis factor alpha (TNF alpha), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, IL-8, and monocyte chemoattractant protein. Polyethylene debris surrounded by macrophages and phagocytosis of debris by macrophages was frequently observed in the interface tissue. Macrophage activation and the production of inflammatory cytokines such as IL-1 and TNF alpha might induce the development of interface tissue. Expression of chemokine mRNAs was also commonly seen, suggesting that this led to recruitment of macrophages into the bone-cement interface tissue. Debris released from implants appears to cause activation of macrophages and the production of inflammatory cytokines and chemokines that induce cellular recruitment into interface tissue. This mechanism might form a vicious cycle that aggravates THA loosening.
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PMID:Macrophage activation and migration in interface tissue around loosening total hip arthroplasty components. 913 74

The chemokines are a homologous serum protein family characterized by their ability to induce activation of integrin adhesion molecules and leukocyte migration. Chemokines interact with their receptors, which are composed of a single-chain, seven-helix, membrane-spanning protein coupled to G proteins. Two CC chemokine receptors, CCR3 and CCR5, as well as the CXCR4 chemokine receptor, have been shown necessary for infection by several HIV-1 virus isolates. We studied the effect of the chemokine monocyte chemoattractant protein 1 (MCP-1) and of a panel of MCP-1 receptor (CCR2)-specific monoclonal antibodies (mAb) on the suppression of HIV-1 replication in peripheral blood mononuclear cells. We have compelling evidence that MCP-1 has potent HIV-1 suppressive activity when HIV-1-infected peripheral blood lymphocytes are used as target cells. Furthermore, mAb specific for the MCP-1R CCR2 which recognize the third extracellular CCR2 domain inhibit all MCP-1 activity and also block MCP-1 suppressive activity. Finally, a set of mAb specific for the CCR2 amino-terminal domain, one of which mimics MCP-1 activity, has a potent suppressive effect on HIV-1 replication in M- and T-tropic HIV-1 viral isolates. We conjecture a role for CCR2 as a coreceptor for HIV-1 infection and map the HIV-1 binding site to the amino-terminal part of this receptor. This concurs with results showing that the CCR5 amino terminus is relevant in HIV-1 infection, although chimeric fusion of various extracellular domains shows that other domains are also implicated. We discuss the importance of CCR2 structure relative to its coreceptor role and the role of anti-CCR2 receptor antibodies in the prevention of HIV-1 infection.
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PMID:The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for HIV-1 infection. 923 95

Chemokines secreted by endothelium have been demonstrated to promote leucocyte recruitment to sites of inflammation. In the present study we investigated the effect of the T lymphocyte-secreted cytokine interleukin (IL)-13 on endothelial expression of chemokines. Employing in situ hybridization and enzyme-linked immunosorbent assay (ELISA) techniques we demonstrate that IL-13, which shares many of its activities with IL-4, selectively induces expression of the C-C chemokine monocyte chemoattractant protein (MCP)-1 in human umbilical vein endothelial cells (HUVEC). However, it fails to up-regulate other C-C and C-X-C chemokines potentially inducible in endothelium such as RANTES (regulated on activation, normal T expressed and secreted), gro-alpha, or IL-8. IL-13 dose-dependently induces monocyte chemotactic activity by HUVEC which can be efficiently blocked by neutralizing antisera against MCP-1. In contrast to the synergistic effect of IL-13 and tumour necrosis factor-alpha (TNF-alpha) on endothelial vascular cell adhesion molecule-1 (VCAM-1) surface expression, TNF-alpha-induced secretion of MCP-1 is not augmented by IL-13. Studying the signalling pathway activated by IL-13 it is demonstrated that a neutralizing monoclonal antibody (mAb) to the 140,000 MW component of the IL-4 receptor (IL-4R alpha) inhibits the effect of IL-13. Immunoprecipitation studies reveal that endothelial IL-4R alpha is rapidly tyrosine phosphorylated upon treatment with IL-13 and IL-4. We furthermore show that both cytokines activate the signal transducer and activator of transcription (Stat) protein-6 in endothelial cells. Our data suggest that IL-13 partly utilizes components of the IL-4 receptor signalling pathway for induction of endothelial MCP-1 expression to facilitate recruitment of blood leucocytes.
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PMID:Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation. 930 36

The course of infection with Leishmania parasites is determined by the type of the developing CD4+ T cell immune response. Macrophages and Langerhans cells/dendritic cells play a decisive role in the interaction between the parasites and the host's immune system because they serve as host cells, as accessory cells that present parasite antigen, deliver costimulatory signals and secrete cytokines modulating the T cell activity and as effector cells eliminating the microorganisms. Therefore, we put particular emphasis on characterizing the role of these cells in cutaneous leishmaniasis and the factors regulating their activities. Our results show that (1) expression of the chemokine monocyte chemoattractant protein 1 (MCP-1) is associated with macrophage infiltration into the lesion and stimulation of leishmanicidal activity, (2) Langerhans cells are required for the transport of Leishmania from the infected skin to the draining lymph node and initiation of the specific T cell immune response in the early phase of infection, (3) lymph node dendritic cells containing persistent parasites may be involved in the maintenance of specific immunity, (4) Langerhans cells are able to present L. major LPG to T cells and (5) treatment of mice with antigen-pulsed Langerhans cells induces protective immunity against cutaneous leishmaniasis.
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PMID:The role of chemokines and accessory cells in the immunoregulation of cutaneous leishmaniasis. 930 4

Type 1 (IFN-gamma/TNF-dominant) and 2 (IL-4/IL-5-dominant) granulomatous inflammation were analyzed in mice with knockout of IFN-gamma or IL-4 genes. Lung granulomas were elicited by beads coated with purified protein derivative (PPD) of Mycobacteria bovis or soluble Schistosoma mansoni egg Ags. Parameters included granuloma size, composition, and macrophage function; white blood cell differentials; lymph node cytokine profiles; and cytokine/chemokine mRNA expression by lungs. Type 1 (PPD) and 2 (soluble Schistosoma mansoni egg Ags) responses showed characteristic cytokine and chemokine profiles in control mice. IFN-gamma knockout converted the PPD response to a type 2-like pattern with eosinophil infiltration and decreased TNF and RANTES, but increased IL-4, IL-5, IL-10, IL-13, monocyte chemoattractant protein-3 (MCP-3), and eotaxin expression. IL-4 knockout exacerbated type 1 inflammation with increased IL-2/IFN-gamma production by lymph nodes and IL-1 production by granuloma macrophages, but unexpectedly, IFN-gamma transcripts were reduced in lungs. Regarding the type 2 response, IL-4 was needed for maximal blood eosinophilia, but surprisingly, its absence had a minimal effect on type 2 granuloma size and composition despite regional reductions of IL-5 and IL-10 as well as local reductions of TNF-alpha, MCP-1, MCP-3, and eotaxin. Thus, the type 2 granuloma was not converted to a type 1 composition with IL-4 knockout, but showed persistent expression of IL-13 and some degree of IL-5 and MCP-3, suggesting that these cytokines could potentially support a compensatory type 2 response. IFN-gamma knockout did not augment type 2 granuloma size or Th2 cytokines in lymph nodes and unexpectedly reduced IL-4 transcripts in lungs. This study offers important implications regarding inflammation and its relationship to local and regional cytokine expression.
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PMID:Mycobacterial and schistosomal antigen-elicited granuloma formation in IFN-gamma and IL-4 knockout mice: analysis of local and regional cytokine and chemokine networks. 931 56

Monocyte chemotactic and activating factor/monocyte chemoattractant protein (MCAF/MCP-1) is a member of the beta (C-C) subfamily of chemokines. The biological roles played by MCAF/MCP-1 in a number of inflammatory and noninflammatory diseases states is not well known. Several studies have confirmed that inflammation is present in the airways of subjects with atopic asthma and with chronic bronchitis. Analysis of bronchoalveolar lavage fluid (BALF) is an effective method of sampling lower respiratory tract inflammation. The aim of this study was to examine associations among MCAF/MCP-1, BALF cells and spirometry parameters and bronchial hyperresponsiveness in patients with atopic asthma and chronic bronchitis. Twenty patients with atopic asthma, 10 patients with chronic bronchitis and 10 patients of the control group, took part in this study. An ELISA test was used to assess MCAF/MCP-1 in BALF. The levels of MCAF/ MCP-1 (mean +/- SEM) were 150 +/- 18.6 pg/ml in patients with atopic asthma, 320 +/- 39.7 pg/ml in chronic bronchitis and 74.9 +/- 3.3 pg/ml in the control group (p < 0.05). When all patients with disease were considered, there was negative correlation with FEF50 (Kendall's correlation coefficient = - 0.4; p < 0.01). Regression analysis has shown that a level of MCAF/MCP-1 over 100 pg/ml was correlated with duration of illness (Pearson's correlation coefficient = 0.7; p < 0.02). In conclusion, MCAF/MCP-1 probably possesses proinflammatory properties in atopic asthma and chronic bronchitis. The elevated level of this chemokine may support the clinical suspicion of specific diagnosis.
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PMID:Monocyte chemotactic and activating factor/monocyte chemoattractant protein (MCAF/MCP-1) in bronchoalveolar lavage fluid from patients with atopic asthma and chronic bronchitis. 933 Jan 91


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