Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines are a superfamily of structurally related cytokines involved in leukocyte recruitment in normal and neoplastic tissues. The availability of non-cross-reacting reagents specific for each member of the C-C and C-X-C family is important for careful characterization of their in vitro and in vivo production and relevance. Here we describe a novel, highly specific, mAb against monocyte chemotactic protein-1 (MCP-1). The 5D3-F7 mAb (IgG1,kappa) recognizes human recombinant and natural MCP-1 in ELISA, immunoprecipitation and immunoblot analysis. As a source of natural MCP-1 we used the 8387 human sarcoma line which produces spontaneously MCP-1 and responds to TNF with increased expression and release. The 5D3-F7 mAb inhibited the chemotactic activity of MCP-1 for monocytes. Using the 5D3-F7 mAb and a polyclonal rabbit anti-MCP-1 serum, a sandwich ELISA was developed. In both the direct and the sandwich ELISA, the 5D3-F7 mAb recognized human MCP-1, but not the closely related C-C chemokines MCP-1, MCP-2, MCP-3, MIP-1 alpha, and RANTES and the C-X-C chemokines IL-8, gro alpha and NAP-2. In culture supernatants the sensitivity of the sandwich ELISA was approximately equal to 30 pg/ml. The sandwich ELISA permitted detection of MCP-1 in resting or cytokine-stimulated endothelial, mesothelial and Kaposi's sarcoma cells. Preliminary immunohistochemical analysis revealed production of MCP-1 by macrophage-like cells at sites of inflammation. The 5D3-F7 mAb provides a novel, highly specific reagent with which to investigate the in vitro and in vivo production and role of MCP-1.
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PMID:A new monoclonal antibody (5D3-F7) which recognizes human monocyte-chemotactic protein-1 but not related chemokines. Development of a sandwich ELISA and in situ detection of producing cells. 808 29

The responses of cloned human NK cells (ERNK57) to seven CC chemokines (monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and 1309) and two CXC chemokines (IL-8 and IP-10) were studied. Except for 1309, all CC chemokines induced chemotaxis of the NK cells in vitro, whereas the CXC chemokines were inactive. Maximal activity was obtained at 1 nM for MCP-1 and 10 to 100 nM for the other CC chemokines. The response showed a typically bimodal concentration dependence in all cases, except for RANTES, which induced a linear increase of migration over the concentration range of 0.1 to 1000 nM. A transient rise of the cytosolic-free Ca2+ concentration ([Ca2+]i), which is characteristic for chemokine-stimulated leukocytes, was observed in NK cells after stimulation with all six active chemokines. Since granule exocytosis is required for NK cell-dependent target killing, the effect of CC chemokines on exocytosis was tested. All CC chemokines that induced chemotaxis and [Ca2+]i changes also induced the release of granzyme A and N-acetyl-beta-D-glucosaminidase from cloned and blood NK cells, as well as CD8+ T cells after pretreatment with cytochalasin B. Maximum release was obtained from NK cells, and amounted to 35% and 13% of the total content of granzyme A and N-acetyl-beta-D-glucosaminidase, respectively. The capacity of cloned NK cells and CD8+ T cells to respond to chemokines depended on the time in culture after stimulation with PHA in the presence of irradiated feeder cells, and maximum responses were observed after 10 to 16 days. Our results demonstrate that CC chemokines activate NK cells, and are, therefore, not only attractants for monocytes, T lymphocytes, and eosinophil and basophil granulocytes.
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PMID:Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release. 859 80

Because dendritic cells (DC) are the most potent antigen-presenting cells involved in many pathophysiological responses, we investigated the effect of chemokines on the migration of these cells in an effort to determine whether chemokines may contribute to the initiation of immune responses. CD34+ progenitor cells isolated from umbilical cord blood were grown in suspension cultures with cytokines and expanded 50- to 100-fold. A variable proportion of the cells expressed markers consistent with DC. The proportion of CD1a+ DC was increased when the cells were cultured with interleukin-4 (IL-4). These cells expressed specific binding sites for C-C and C-X-C chemokines. Cells cultured with or without IL-4 had similar binding profiles. All C-C chemokines tested, including monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein-1 alpha (MIP1 alpha), MIP-1 beta, and RANTES, induced migration of DC-enriched cells cultured with or without IL-4 with MCP-3 being the most potent chemoattractant. Phenotypic analysis of cell migrating in response to C-C chemokines showed that CD1a+ cells were indeed attracted across the polycarbonate filters, and there was no preferential attraction of contaminating CD14+ monocytes by C-C chemokines. DC-enriched cells also expressed specific binding sites for IL-8 and NAP2, which failed to induce cell migration. Our results suggest that C-C chemokines may participate in the recruitment of DC to amplify host defense.
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PMID:Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro. 883 Jul 93

The majority of synovial fluids from 29 rheumatoid arthritis patients were strongly attractive for normal blood lymphocytes judged by assays of polarization and collagen gel invasion. While rheumatoid synovial fluids contained IL-15, IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) at levels sufficient to attract lymphocytes, inhibition of the activity of any single cytokine using specific antibody did not abolish the activity of the fluid. However combinations of anti-cytokine antibodies used together (anti-IL-15+anti-MCP-1; anti-IL-8+anti-MCP-1 or +anti-MIP-1 alpha) inhibited most of the activity, suggesting that attraction of lymphocytes by the fluids is due to a combination of attractants. Blood lymphocytes required activation by overnight culture to respond optimally, while rheumatoid synovial tissue lymphocytes responded to synovial fluids without a requirement for a period of culture. Lymphocytes derived from rheumatoid synovial fluids were poorly responsive to locomotor stimulants. Most of the responding cells from blood mononuclear cell fractions were T lymphocytes of the CD45RO isotype. Incubation in the presence of cyclosporin A or corticosteroids inhibited the response of lymphocytes to the fluids, but the presence of non-steroidal anti-inflammatory drugs (NSAIDs) and other agents used in therapy of the patients from whom the fluids were taken had no inhibitory effect.
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PMID:The chemoattractant activity of rheumatoid synovial fluid for human lymphocytes is due to multiple cytokines. 891 67

Allograft rejection is the main cause of corneal graft failure. T lymphocytes and macrophages have been implied to be involved in corneal rejection, but little is known about the molecular mechanism in this process. In this study, cytokine mRNA expression in the cornea was analysed during experimental corneal transplantation. The donor and acceptor corneas of two groups of rats were studied after receiving an allo- (PVG to AO rat) or autograft (AO rat). For controls, central buttons and peripheral corneal rings of the non-transplanted contralateral eyes were used. At different post-operative days (1, 3, 7, 12 and 19), the corneas were removed and subjected to mRNA isolation. All corneal samples underwent semi-quantitative reverse transcriptase-polymerase chain reaction analysis for interleukin-1 beta, interleukin-1, receptor antagonist, interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-alpha, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA expression. Corneal rejection, characterized by opaque corneas with prominent neovascularization, was always diagnosed around day 12. Contralateral, non-grafted corneas showed constitutive mRNA expression for interleukin-1 receptor antagonist and in a few samples also monocyte chemotactic protein-1 and macrophage inflammatory protein-2 mRNA was found. Both allo- and autografts expressed mRNA for the cytokines found in contralateral, non-grafted tissue, as well as for interleukin-1 beta, interleukin-6, interleukin-10 and tumor necrosis factor-alpha. In allografts, the mRNA levels for these cytokines remained constant throughout all post-operative days, with increased interleukin-6 mRNA expression after post-operative day 12. The analysis of the autografts revealed high cytokine mRNA levels until post-operative day 3 or 7, which decreased from then on, except for interleukin-1 receptor antagonist. mRNA for interleukin-2, interleukin-4 and interferon-gamma was not observed in autografts at any time point and in allografts, until post-operative day 12. Interleukin-2 and interferon-gamma mRNA showed maximal expression on POD 12, while in autografts, a marked decrease was observed after POD 3. IL-10 mRNA levels decreased immediately after POD 1 in autografted eyes. For TNF-alpha, an increased mRNA expression starting on POD 7 was found in recipient rings of allografted eyes, while in autografts a weak expression was seen in some samples. MIP-2 transcription increased on PAD 12, while in autografts, its expression was not markedly different from that detected in the contralateral, non-grafted peripheral cornea.
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PMID:Cytokine mRNA expression during experimental corneal allograft rejection. 894 52

Thymic peptides show immunoreconstitutive und tumor suppressive effects. They are used in oncology to improve the immunological status of patients. Chemokines are able to activate immune cells and inhibit tumor growth. In this study it was proved whether low molecular thymic peptides are able to increase the secretion of the chemokines monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), macrophage inflammatory protein-1 alpha (MIP-1 alpha) and macrophage inflammatory protein-1 beta (MIP-1 beta) as well as the cytokine tumor necrosis factor-alpha (TNF-alpha) which is not related to chemokines using cell cultures of human whole blood. The thymic peptides induced a significant (p < 0.05) elevated secretion of MCP-1 and IL-8 whereas for MIP-1 alpha, MIP-1 beta and TNF-alpha no significant chances were seen. MCP-1 and IL-8 showed divergent dose-dependent effects and a different time kinetic of their secretion. The MCP-1 concentration correlated positively with the count of monocytes in whole blood of the volunteers while the IL-8 concentration in dependence with the incubation time correlated positively with the count of granulocytes or monocytes of the volunteers. The results indicate an activation of monocytes and/or granulocytes by low molecular thymic peptides followed by selective elevated secretion of MCP-1 and IL-8.
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PMID:[The in vitro induction of monocyte chemotactic protein-1 and interleukin-8 in whole human blood by low molecular weight thymus peptides]. 899 63

The appearance of polymorphonuclear and mononuclear leukocytes in the cerebrospinal fluid (csf) is an important hallmark of bacterial meningitis. Chemokines are candidate mediators of cell migration from blood into the subarachnoid space. Therefore, concentrations of C-X-C and C-C chemokines in the csf of patients with pyogenic meningitis were measured by ELISA. Highly significant elevations of chemokine levels in comparison with noninflammatory csf controls were found for IL-8 (median, 21.6 ng/ml; range, < 0.1 to 191.3), growth-related gene product alpha (median, 5.6 ng/ml; range, < 0.1 to 48.2), monocyte chemotactic protein-1 (median, 26.4 ng/ml; range, < 0.2 to 193.8), macrophage inflammatory protein-1 alpha (MIP-1 alpha; median, 1.8 ng/ml; range, < 0.5 to 18.0), MIP-1 beta (median, 10.6 ng/ml; range, < 0.3 to 84.4), but not for RANTES (regulated upon activation, normal T cell expressed and secreted). The csf of bacterial meningitis were chemotactic for neutrophils and mononuclear leukocytes. Correlation analysis demonstrated a strong association between individual chemokine levels and chemotactic activity mediated by csf. A significant reduction of neutrophil chemotaxis was obtained by anti-IL-8 and anti-growth-related gene product alpha Abs, and a reduction of mononuclear cell migration was achieved by a combination of anti-monocyte chemotactic protein-1, anti-MIP-1 alpha, and anti-MIP-1 beta Abs. Since no significant correlation was found between csf leukocyte counts and chemokine concentrations or chemotactic activity mediated by csf, additional factors influence the extent of pleocytosis in vivo.
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PMID:C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro. 902 38

Chemokines may be important in the pathogenesis of leukocyte infiltration in tubulointerstitial nephritis associated with glomerular disease. We studied the renal cortical expression of the C-C (macrophage inflammatory protein-1alpha (MIP-1alpha)), monocyte chemotactic protein-1 (MCP-1), and RANTES) and C-X-C (interferon-inducible protein-10 (IP-10), MIP-2, and cytokine-induced neutrophil chemoattractant (CINC)) chemokines 4, 6, 8, 10, 14, and 21 days after the induction of puromycin aminonucleoside (PAN) nephrosis. There was a 7- to 10-fold increase in the steady state mRNA expression of IP-10 and MCP-1 in the renal cortex of rats 6 to 8 days after the administration of PAN that declines thereafter reaching control values by day 21. The site of IP-10 and MCP-1 mRNA production was localized to intrinsic tubulointerstitial cells and not to infiltrating monocytes or macrophages. By comparison, there was a low basal expression of RANTES mRNA in the renal cortex of nephrotic rats that did not differ from those of control rats. In contrast, CINC, MIP-2, and MIP-1alpha mRNAs were not detected. Translation of MCP-1 mRNA into protein was confirmed with an ELISA. These changes in chemokine gene expression were associated with a tubulointerstitial T lymphocyte and macrophage infiltration beginning on day 6 that peaked on day 10. Administration of a neutralizing Ab to rat MCP-1 (n = 5) beginning on day 4 resulted in a 45% decline in tubulointerstitial macrophage infiltration from 8.4 +/- 1.3% to 4.6 +/- 0.4% (p < 0.001) on day 6. These data provide evidence that MCP-1, and possibly IP-10, are important in the pathogenesis of monocyte/macrophage infiltration in the tubulointerstitial nephritis associated with PAN nephrosis.
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PMID:Chemokine expression in experimental tubulointerstitial nephritis. 921 6

Chemokines are pivotal in the trafficking of leukocytes. In the present study, we examined the expression of multiple chemokine genes during the course of lymphocytic choriomeningitis (LCM) in mice. In noninfected mice, no detectable chemokine gene expression was found in the brain; however, by day 3 postinfection, the induction of a number of chemokine mRNAs was observed as follows (in order from the greatest to the least): cytokine responsive gene-2 or interferon-inducible 10-kDa protein (Crg-2/IP-10), RANTES, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1beta), and MCP-3. At day 6 postinfection, the expression of these chemokine mRNAs was increased, and low expression of lymphotactin, C10, MIP-2, and MIP-1alpha mRNAs was detectable. Transcript for T-cell activation-3 was not detectable in the brain at any time following LCM virus (LCMV) infection. With some exceptions, a pattern of chemokine gene expression similar to that in the brain was observed in the peripheral organs of LCMV-infected mice. Mice that lacked expression of gamma interferon developed LCM and had a qualitatively similar but quantitatively reduced cerebral chemokine gene expression profile. In contrast, little or no chemokine gene expression was detectable in the brains of LCMV-infected athymic mice which did not develop LCM. Expression of Crg-2/IP-10 RNA was localized to predominantly resident cells of the central nervous system (CNS) and overlapped with sites of viral infection and immune cell infiltration. These findings demonstrate the expression of a number of chemokine genes in the brains of mice infected with LCMV. The pattern of chemokine gene expression in LCM may profoundly influence the characteristic phenotype and response of leukocytes in the brain and contribute to the immunopathogenesis of this fatal CNS infection.
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PMID:Chemokine gene expression in the brains of mice with lymphocytic choriomeningitis. 931 71

On infection of the cornea with herpes simplex virus (HSV), an immunopathologic response termed herpetic stromal keratitis (HSK) ensues. This response is mediated primarily by CD4+ T cells and only occurs if mice are infected with replication-competent virus, although replication-defective mutants induce cellular immune responses following infection. To determine the consequences of HSV replication in the cornea, which is crucial for HSK manifestation, corneas infected with productive virus and replication-defective mutants were analyzed for chemokines and proinflammatory cytokine mRNA expression by RT-PCR at various times. While productive infection resulted in rapid upregulation and sustained expression of such chemokines as N51/KC, macrophage inflammatory protein-1beta (MIP-1beta), MIP-2, and monocyte chemotactic protein-1 (MCP-1) and such cytokines as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor-alpha (TNF-alpha), expression of such inflammatory mediators was minimal and transient after unproductive infection. Expression of MIP-1alpha and lymphotactin along with a biphasic expression of IL-6 and MIP-2 were seen only with productive infection. Initial PMN recruitment into the cornea was approximately 50-fold greater with productive infection than with unproductive infection. These data suggest that a replication-induced proinflammatory milieu in the cornea is crucial for the subsequent progression of HSK possibly because of enhancement of the expression of corneal agonists that drive HSK manifestation.
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PMID:Herpes simplex virus replication-induced expression of chemokines and proinflammatory cytokines in the eye: implications in herpetic stromal keratitis. 978 6


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