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)

We have examined the role of monocyte chemoattractant protein 1 (MCP 1) in the pathogenesis of monocyte/macrophage-dependent IgA immune complex alveolitis in the rat. Rat MCP 1 was cloned and expressed in order to facilitate analysis of its function in rat models of human disease. A cDNA library was constructed from rat pulmonary artery endothelial cells stimulated with TNF-alpha. The cDNA library was screened with synthetic oligonucleotide probes based on the recently published rat MCP 1 cDNA sequence. Among numerous MCP 1-positive clones, four full length (approximately 480 bp) cDNA were rescued, amplified by polymerase chain reaction, and ligated into a pJVETLZ baculovirus transfer vector. Spodoptera frugiperda insect cells (Sf-21) infected with baculovirus recombinants (Auto-grapha california nuclear polyhedrosis virus) bearing properly oriented MCP 1 cDNA (AcMCP 1) directed the expression of unique peptides of 18, 21, and 23 kDa. Treatment of AcMCP 1-infected Sf-21 cells with tunicamycin resulted in reduced production of the 21- and 23-kDa proteins and an increase in 16- to 18-kDa products, the predicted size range of uncleaved and nonglycosylated rat MCP 1. Denatured and refolded 23-kDa and 21-kDa rat MCP 1 species exhibited dose-dependent monocyte-specific chemotactic activity at concentrations as low as 10(-10) M whereas the 18-kDa species exhibited negligible activity. Antibodies that react with the immunoblot, block rat rMCP 1-directed monocyte chemotaxis, and neutralize monocyte-specific chemotactic activity secreted by TNF-stimulated rat endothelial cells were raised in rabbits immunized with the 23-kDa MCP 1 species. Intravenous administration of anti-MCP 1 antibodies upon initiation of IgA immune complex lung injury resulted in a marked reduction in lung injury as measured by pulmonary vascular permeability, alveolar hemorrhage, and pulmonary monocyte/macrophage recruitment and pulmonary monocyte/macrophage recruitment. These data suggest that MCP 1 may play an important role in the pathogenesis of monocyte/macrophage-dependent IgA immune complex alveolitis in the rat.
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PMID:Potential role of monocyte chemoattractant protein 1/JE in monocyte/macrophage-dependent IgA immune complex alveolitis in the rat. 138 71

Experimental evidence is accumulating to support a central role for cytokines in the pathophysiology of hemolytic transfusion reactions. The production of tumor necrosis factor, interleukin-8, and monocyte chemoattractant protein occurs in whole blood in response to ABO incompatible red cells, a model of acute hemolytic transfusion reactions. Peripheral blood mononuclear cells may produce interleukin-1 beta, tumor necrosis factor, interleukin-8, monocyte chemoattractant protein, and interleukin-1 receptor antagonist in response to IgG-coated red cells, a model of delayed hemolytic transfusion reactions. Cultured umbilical vein endothelial cells respond to conditioned plasma from ABO-incompatibility reactions by expressing the procoagulant tissue factor and the leukocyte adhesion molecules ELAM-1 and ICAM-1. These in vitro endothelial cell responses can be inhibited by neutralizing antibodies to tumor necrosis factor, suggesting that TNF may have a central role in intravascular coagulation and end-organ injury that may occur in acute hemolytic transfusion reactions.
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PMID:The role of cytokines in hemolytic transfusion reactions. 771 93

Using a rat lung organ culture system, we analyzed the role of monocyte chemoattractant protein 1 (MCP 1) in leukocyte to lung adhesive interactions and monocyte-mediated lung injury. Quantitative leukocyte to lung adhesive interactions were examined using an adaptation of the Woodruff-Stamper frozen section binding assay. Pretreatment of organ cultures with recombinant human tumor necrosis factor (rhTNF alpha) resulted in a protein synthesis-dependent increase in the adhesiveness of lung tissue for peripheral blood monocytes. Adhesion of monocytes to lung tissue was not increased above baseline after 7 hours but increased more than twofold by 24 hours and persisted through 48 hours. Binding of monocyte to lung tissue was further increased when recombinant rat MCP 1 was added to monocyte suspensions immediately before being layered onto lung sections derived from either TNF alpha-treated or untreated organ cultures. Addition of antibody directed against rat CD11b/c resulted in a moderate reduction in monocyte binding. TNF or lipopolysaccharide-induced activation of mononuclear cells in the presence of [3H]leucine-labeled organ cultures resulted in lung injury as assessed by radioisotope release. Mononuclear cell-mediated organ culture injury could be partially inhibited with anti-rat MCP 1 antibody, anti-rat CD11b/c antibody, or antioxidants including catalase and deferoxamine. Anti-MCP 1 and anti-CD11b/c increased the absolute numbers of monocytes that could be retrieved from monocyte-lung co-cultures while catalase and deferoxamine did not. In vitro studies revealed that isolated rat peripheral blood monocytes produce O2- in response to MCP 1. These data provide a functional correlate for recent in vitro studies which suggest that MCP 1 may mediate leukocyte adhesive processes by up-regulating beta 2 integrin expression on monocytes. This study provides evidence that monocytes activated by MCP 1 can damage lung tissue through an oxidant-mediated mechanism. Monocyte chemoattractant protein 1 may participate in the pathogenesis of monocyte-mediated lung injury by modulating inflammatory cell adhesion as well as through monocyte activation.
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PMID:Analysis of monocyte chemoattractant protein 1-mediated lung injury using rat lung organ cultures. 810 96

We have isolated a cDNA (NC28) transcribed from a mRNA which is transiently induced in U937 promonocytic cells by PMA and super-induced by cycloheximide. NC28 cDNA encodes a new member of the chemokine family, MCP-3, recently purified from MG-63 osteosarcoma cells by Van Damme et al. [1]. The MCP-3 protein sequence shows 74% identity with human monocyte chemoattractant protein 1 (MCP-1) and, like MCP-1, recombinant MCP-3 protein shows chemotactic activity for monocytes but not for neutrophils. However the secreted MCP-3 protein differs from MCP-1 in being N-glycosylated. The 3' noncoding regions of MCP-3 and MCP-1 mRNAs are more diverged (44%), allowing specific cDNA probes to be made, and indicating that the two genes are evolutionarily distant. Sequence comparisons of the 3' noncoding regions suggest that MCP-3 may be the human homologue of the mouse MARC gene [2], and that MCP-1 and MCP-3 genes arose by a gene duplication event before the mammalian radiation. Both MCP-1 and MCP-3 mRNAs are expressed by PBMC, principally by monocytes, with MCP-1 mRNA being expressed at levels 2-4 times that of MCP-3 mRNA. However, while MCP-1 mRNA is also expressed at high levels in fibroblast or astrocytoma cell lines after IL-1 and TNF stimulation, MCP-3 mRNA is expressed only at very low levels in these cells. The cellular origin of MCP-3 is thus more restricted than that of MCP-1. In our experiments on PBMC, LPS is not a consistent inducer of MCP-1 and MCP-3 mRNAs. In some experiments, it actually decreases levels of these two mRNAs, while concomitantly increasing IL-6 and TNF-alpha mRNA levels. Levels of MCP-1 and MCP-3 mRNAs in PBMC are both increased by IFN-gamma, although IL-6 mRNA is not induced. They are also increased by PHA-P and are decreased, in most cases, by IL-13 [3]. MCP-1 and MCP-3 mRNAs are thus co-ordinately regulated in monocytes in response to a number of inducing or inhibitory agents, in a manner differing in several respects from that of other monokines such as IL-6.
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PMID:Molecular cloning of the MCP-3 chemokine gene and regulation of its expression. 831 76

The aim of this study was to determine the dose-response relationship between cigarette smoke exposure and pulmonary cell and cytokine concentrations in bronchoalveolar lavage (BAL). BAL cells and BAL supernatant concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 from 14 healthy smokers and 16 healthy nonsmokers were quantified. Statistically greater concentrations of neutrophils, macrophages, IL-1 beta, IL-6, IL-8 and MCP-1 were observed among smokers compared with nonsmokers (p < or = 0.0007 in all cases). Cigarette smoking, categorized ordinally as: less than one pack, one pack, or greater than one pack per day, was predictive of BAL macrophages (p < 0.0001), neutrophils (p = 0.015), IL-1 beta (p < 0.001) and IL-8 (p = 0.02). We conclude that concentrations of macrophages, neutrophils, IL-1 beta and IL-8 are elevated in the pulmonary microenvironment of smokers in a cigarette dose-dependent manner. Based on the present findings, we would caution against simple analyses that treat current smokers as a homogeneous group and which do not account for smoking intensity.
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PMID:Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. 890 55

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

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

Chemokines are low molecular weight secretory proteins that function principally as stimulators of leukocyte recruitment. There are four defined chemokine subfamilies based on their primary structure, CXC, CC, C and CX3C. Members of the CC chemokine subfamily, a such as monocyte chemoattractant protein 1 (MCP-1) are chemotactic for monocytes and other leukocyte subsets. Because monocytes produce factors that regulate bone formation or resorption, such as PDGF, IL-1 or TNF, chemokines that initiate their recruitment are likely to be important in regulating osseous metabolism. In the studies below, data is presented demonstrating mechanisms of MCP-1 expression in osteoblastic cells. These studies establish that MCP-1 is induced during osseous inflammation and in developmentally regulated bone remodelling, and is associated with enhanced monocyte recruitment when applied to osseous lesions.
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PMID:The expression of monocyte chemoattractant protein-1 and other chemokines by osteoblasts. 1039 26

The expression of chemokines, including monocyte chemoattractant protein (MCP)-1, by many cell types contributes to the pathogenesis of inflammatory diseases. We examined MCP-1 expression in human umbilical vein endothelial cells (EC) following cytokine treatment. We specifically compared the effect of TGF-beta 1 on this cytokine-induced expression, as TGF-beta has been shown to have immunosuppressive effects on EC. EC expressed MCP-1 mRNA and protein in response to TNF alpha, IFN gamma or IL-1beta, but not TGF-beta1. TGF-beta1 in cotreatment with either TNF alpha or IL-1beta, but not IFN gamma, significantly decreased MCP-1 mRNA and protein expression, as compared to TNF alpha or IL-1beta treatment alone. Pretreatment with TGF-beta had no effect on any cytokine-induced MCP-1 expression. TGF-beta had no effect on MCP-mRNA stability. Examination of TNF receptor expression by flow cytometry revealed that TNF alpha treatment caused a decrease of p75 expression on the cell surface. The p55 receptor was not detected at the cell surface, but was localized intracellularly by confocal microscopy. Treatment of EC with TGF-beta alone decreased p75 surface expression and in cotreatment with TNF alpha, caused an additive decrease in p75 surface expression, as compared to TNF alpha treatment alone. Whereas mRNA expression for both receptors was increased with TNF alpha treatment, this was decreased with TGF-beta/TNF alpha cotreatment, as compared to TNF alpha treatment alone. Thus, the expression of TNF receptors was also down-modulated by TGF-beta. These findings indicate additional mechanisms by which TGF-beta exerts immunosuppressive properties on EC.
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PMID:TGF-beta downmodulates cytokine-induced monocyte chemoattractant protein (MCP)-1 expression in human endothelial cells. A putative role for TGF-beta in the modulation of TNF receptor expression. 1047 92

Airway epithelium participates in inflammatory reactions by producing chemokines and expressing cell-surface adhesion molecules which aid in the selective recruitment of effector cells. Previous studies showed that proinflammatory cytokines, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF alpha), induce surface expression of intercellular adhesion molecule 1 (ICAM-1) and the production of the chemokines interleukin 8 (IL-8) and monocyte chemoattractant protein (MCP-1) on pulmonary epithelial cell lines in vitro. In this study, the dose response of four cytokines, IL-1alpha, IL-1beta, TNF alpha and TNF beta, in inducing ICAM-1 expression and production of IL-8 and MCP-1 on pulmonary A549 epithelial cells was examined. Both IL-1alpha and IL-1beta induced ICAM-1 expression and IL-8 and MCP-1 production at lower doses than TNF alpha or TNF beta. Pentoxifylline, an anti-inflammatory agent used to treat vascular diseases, was tested for its ability to inhibit the activation of airway epithelial cells by these cytokines. Pentoxifylline completely inhibited the surface expression of ICAM-1 and the production of IL-8 and MCP-1 by cytokine-activated epithelial cells. As elevated levels of chemokines are often present in bronchial lavage fluids of patients suffering from various acute respiratory diseases, pentoxifylline may be useful for preventing the rapid development of immune reactions leading to lung injury.
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PMID:Pentoxifylline inhibits ICAM-1 expression and chemokine production induced by proinflammatory cytokines in human pulmonary epithelial cells. 1074 5


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