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 investigated the involvement of monocyte chemoattractant protein (MCP)-1 in a murine model of septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies demonstrated that CLP induced a dramatic increase in MCP-1 production in the peritoneum, followed by an increase in the recruitment of leukocytes. MCP-1 blockade with anti-MCP-1 antiserum significantly decreased the survival rate following CLP, which was accompanied by an enhanced recovery of viable bacteria from the peritoneum. This was likely due to the reduction in the recruitment and activation of both macrophages and neutrophils. To understand the mechanisms whereby MCP-1 may influence neutrophil infiltration, levels of chemokines known to attract neutrophils were monitored, which showed that peritoneal levels of macrophage-inflammatory protein (MIP)-2, KC, and MIP-1alpha were not altered with anti-MCP-1 Abs. However, anti-MCP-1 Abs reduced the peritoneal levels of leukotriene B4 (LTB4) by 59%. The i.p. injection of MCP-1 into normal mice resulted in elevated levels of LTB4 in the peritoneum. In vitro, MCP-1 stimulated the production of LTB4 from peritoneal macrophages, in a dose-dependent manner. A specific LTB4 receptor antagonist (CP-105, 696) inhibited CLP-induced recruitment of both neutrophils and macrophages, which was accompanied by a reduced level of MCP-1 in the peritoneum. Finally, administration of CP-105,696 was extremely detrimental to the survival of mice following CLP. These experiments demonstrate that endogenous MCP-1 serves as an indirect mediator to attract neutrophils via the production of LTB4, and suggest the cross-talk can occur between MCP-1 and the lipid mediator LTB4 during septic peritonitis.
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PMID:Endogenous monocyte chemoattractant protein-1 (MCP-1) protects mice in a model of acute septic peritonitis: cross-talk between MCP-1 and leukotriene B4. 1057 Mar 5

To elucidate the role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein(MCP)-1 in the pathogenesis of rapidly progressive glomerulonephritis (RPGN), we determined the urinary levels of MCAF/MCP-1 in 20 healthy subjects, 30 patients showing RPGN with crescents, and 39 patients with various types of renal diseases without crescents. We divided RPGN into two subgroups, the acute type and the insidious type, with regard to the declination rate of reciprocals of serum creatinine with time as previously reported. In addition, we divided the patients with RPGN into anti-neutrophil cytoplasmic antibody(ANCA)-related diseases and immune complex(IC)-mediated diseases with regard to etiology. Urinary levels of MCAF/MCP-1 were significantly higher in patients with RPGN as compared with those of other renal diseases and healthy volunteers(21.8 +/- 4.5 vs. 11.6 +/- 3.5, 1.0 +/- 0.1 pg/ml creatinine, respectively, p < 0.01, mean +/- SEM). There was no difference in the urinary levels of MCAF/MCP-1 between the acute and insidious types of RPGN patients. In addition, there was no difference in the urinary levels of MCAF/MCP-1 between the patients with ANCA-related and IC-mediated diseases. Urinary levels of MCAF/MCP-1 in patients with RPGN were correlated well with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Immunohistochemical examinations revealed that MCAF/MCP-1 positive cells were detected in tubular epithelial and endothelial cells and mononuclear infiltrated cells in the interstitium. Moreover, elevated urinary MCAF/MCP-1 levels in patients with RPGN, regardless of subgroups, were dramatically decreased during methylprednisolone pulse therapy induced convalescence. These results suggest that MCAF/MCP-1 may be involved in the pathogenesis of RPGN via macrophage recruitment and activation.
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PMID:[The role of monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1 in subgroups of rapidly progressive glomerulonephritis]. 1057 96

Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) B(4)-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an LTB(4)-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung.
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PMID:Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities. 1060 Aug 85

Infiltrating leukocytes may be responsible for autoimmune disease. We hypothesized that the chemokine monocyte chemoattractant protein (MCP)-1 recruits macrophages and T cells into tissues that, in turn, are required for autoimmune disease. Using the MRL-Fas(lpr) strain with spontaneous, fatal autoimmune disease, we constructed MCP-1-deficient MRL-Fas(lpr) mice. In MCP-1-intact MRL-Fas(lpr) mice, macrophages and T cells accumulate at sites (kidney tubules, glomeruli, pulmonary bronchioli, lymph nodes) in proportion to MCP-1 expression. Deleting MCP-1 dramatically reduces macrophage and T cell recruitment but not proliferation, protects from kidney, lung, skin, and lymph node pathology, reduces proteinuria, and prolongs survival. Notably, serum immunoglobulin (Ig) isotypes and kidney Ig/C3 deposits are not diminished in MCP-1-deficient MRL-Fas(lpr) mice, highlighting the requirement for MCP-1-dependent leukocyte recruitment to initiate autoimmune disease. However, MCP-1-deficient mice are not completely protected from leukocytic invasion. T cells surrounding vessels with meager MCP-1 expression remain. In addition, downstream effector cytokines/chemokines are decreased in MCP-1-deficient mice, perhaps reflecting a reduction of cytokine-expressing leukocytes. Thus, MCP-1 promotes MRL-Fas(lpr) autoimmune disease through macrophage and T cell recruitment, amplified by increasing local cytokines/chemokines. We suggest that MCP-1 is a principal therapeutic target with which to combat autoimmune diseases.
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PMID:Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice. 1060 56

It is well known that antrum-predominant gastritis and pan-gastritis occurs in the patients with Helicobacter pylori-positive duodenal ulcer (DU) and gastric ulcer (GU), respectively. However, the role of chemokines in the pathogenesis of these pathologies is unclear. We examined the regional differences in mucosal chemokine production in patients with DU and GU. The production of interleukin-8 (IL-8), growth-related gene (GRO) alpha, and macrophage inflammatory protein (MIP)-1alpha was greater in the antrum than in the corpus in DU patients. In the patients with GU, monocyte chemoattractant protein (MCP)-1 levels in the mucosa adjacent to ulcer were greater than those away for the ulcer in the corpus. The reduction in chemokine production occurring in association with the eradication of H. pylori differed between DU and GU patients in the antrum (IL-8, P = 0.0394; GROalpha, P = 0.0149; MIP-1alpha, P = 0.0246; MCP-1, P = 0.0087). The data imply a different pathogenesis may exist for the gastritis present in patients with DU and GU occurring in H. pylori-positive individuals.
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PMID:Regional differences on production of chemokines in gastric mucosa between Helicobacter pylori-positive duodenal ulcer and gastric ulcer. 1063 Apr 87

Interleukin (IL) 6, an autocrine growth factor for mesangial cells, and chemokines, which are released from activated mesangial cells and induce leukocyte infiltration, play a critical role in the progression of immune system mediated renal diseases. Since the reciprocal relationship between IL-6 and chemokines in renal inflammation has been barely investigated, we have analyzed whether IL-6 (500 ng/ml), alone or in combination with the soluble form of its receptor (sIL-6R, 200 ng/ml), can induce normal human mesangial cells (NHMC) to release alpha and/or beta chemokines: MCP-1 (monocyte chemoattractant protein 1), IL-8, Rantes (regulated on activation, normal T cell expressed and secreted), and MIP-1alpha (macrophage inflammatory protein 1alpha). Whereas IL-6 or sIL-6R alone were ineffective in inducing significant chemokine release from NHMC, the simultaneous treatment with IL-6 and sIL-6R showed a significant interaction, leading to a strong synergic effect on MCP-1 synthesis and release without exerting any relevant activity on IL-8, Rantes, or MIP-1alpha. Consistently with the unresponsiveness to IL-6, mRNA and protein expression analysis of the two subunits which form the functional IL-6 receptor showed that NHMC express only the gp130 signal-transducing chain and not the subunit-specific IL-6R (gp80). These findings support an unexpected role of the IL-6 system in kidney inflammatory reactions through the selective regulation of monocyte recruitment.
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PMID:Selective induction of MCP-1 in human mesangial cells by the IL-6/sIL-6R complex. 1064 81

The recruitment of immunocompetent cells to the site of inflammation represents an essential part of the host defense during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Recently, it was shown that intraperitoneal application of granulocyte macrophage-colony stimulating factor (GM-CSF) leads to a marked transient recruitment of macrophages, paralleled by an increase in monocyte chemoattractant protein (MCP)-1. We, therefore, tested the in vitro effect of GM-CSF on the release of the chemotaxins interleukin (IL)-8 and MCP-1 by human peritoneal macrophages. Cells were stimulated with recombinant GM-CSF for 4, 12, and 20 hours in concentrations ranging from 0.1 to 100 pg/mL. Cells stimulated with lipopolysaccharide (LPS) or unstimulated cells served as control. Recombinant GM-CSF at concentrations found during CAPD peritonitis in vivo significantly increased the release of IL-8 and MCP-1 in a time- and dose-dependent manner. The maximum effect of IL-8 was observed directly after cell isolation, and decreased after a culture period of 10 days. Thus, our results indicate that peritoneal macrophages are the potential source of chemokines released upon GM-CSF stimulation.
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PMID:Granulocyte macrophage-colony stimulating factor stimulates secretion of chemoattractive cytokines by peritoneal macrophages of CAPD patients. 1064 17

The expression of chemokines during an immune response may participate in determining the intensity and type of the developing immune response. In the present study, we have examined the effect of overexpressing monocyte chemoattractant protein (MCP)-1 at the site of immunization during different stages of Th1- and Th2-type granulomatous responses. The overexpression of MCP-1 by MCP-1 adenovirus during the sensitization phase of the purified protein derivative Th1-type model significantly reduced the elicitation of the granulomatous response. In contrast, the overexpression of MCP-1 during the sensitization phase of the schistosome egg Ag Th2 response led to an enhanced granulomatous reaction. When cytokines were examined upon restimulation of splenocytes ex vivo, an altered cytokine profile was observed, as compared with control mice. IFN-gamma and IL-12 were significantly reduced in the purified protein derivative Th1-type response, whereas IL-10 and IL-13 were up-regulated in the schistosome egg Ag Th2-type response. The regulation of the immune response was further examined by using the MCP-1 adenovirus at later time points during the elicitation phase. When MCP-1 was overexpressed during the elicitation phase of the responses, neither the Th1-type nor the Th2-type granuloma was altered. Likewise, the cytokine profiles after restimulation of splenocytes ex vivo were unchanged. Thus, the function of MCP-1 may depend on the stage and type of immune response.
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PMID:Adenoviral-mediated overexpression of monocyte chemoattractant protein-1 differentially alters the development of Th1 and Th2 type responses in vivo. 1065 13

Sixteen healthy subjects were intravenously injected with lipopolysaccharide (LPS), once with placebo and once with recombinant human interleukin (IL)-10 (25 microgram/kg), to determine the effect of IL-10 on LPS-induced production of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1. LPS induced transient increases in serum MIP-1alpha, MIP-1beta, and MCP-1. Pretreatment with IL-10 inhibited LPS-induced release of MIP-1alpha, MIP-1beta, and MCP-1. In whole blood in vitro, the IL-10-induced inhibition of MIP-1alpha and MIP-1beta release was equally potent in the presence or absence of an anti-tumor necrosis factor (TNF) antibody. Although isolated peripheral blood mononuclear cells produced more MIP-1alpha and MIP-1beta than neutrophils, the latter cells were more sensitive to the inhibiting effect of IL-10. IL-10 attenuates LPS-induced production of CC chemokines in human endotoxemia, whereby in vitro experiments suggest that, in the case of MIP-1alpha and MIP-1beta release, this effect is independent from an inhibitory effect on TNF production.
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PMID:Interleukin 10 inhibits the release of CC chemokines during human endotoxemia. 1066 45

Sepsis and septic syndrome represent an intense systemic response with multiple physiologic and immunologic abnormalities, leading to multiple organ failure. Recent investigations suggest that the critical conditions are balanced by endogenous cytokines. In the present study, we examined the involvement of endogenous monocyte chemoattractant protein (MCP)-1 in the regulation of cytokine production in tissue/organs in a murine model of acute septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies showed that CLP induced elevated levels of MCP-1 in tissues, such as liver, lung, and kidney. To neutralize endogenous MCP-1, either anti-MCP-1 antibodies or control antibodies were intraperitoneally administered 2 h prior to CLP. Administration of anti-MCP-1 antibodies resulted in a decrease in the level of interleukin (IL)-13 in tissues, while increasing the level of tumor necrosis factor-alpha, compared to control. In addition, anti-MCP-1 treatment decreased the level of IL-12 and, in contrast, increased the level of IL-10 in specific tissues. These findings suggest that endogenous MCP-1 influences the cytokine balance in tissues in favor of anti-inflammatory and immune-enhancing cytokines, probably protecting the host from tissue/organ damage during sepsis.
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PMID:Endogenous MCP-1 influences systemic cytokine balance in a murine model of acute septic peritonitis. 1071 11


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