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)

Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant of asthma since, unlike extrinsic (atopic) asthma, patients are skin-prick test negative to common aeroallergens and have total serum immunoglobulin E concentrations within the normal range. However both atopic and nonatopic asthma are characterized by chronic inflammation of the bronchial mucosa in which eosinophils are prominent and are believed to be associated with local tissue damage. Therefore, specific eosinophil chemoattractants acting in concert with factors which prolong eosinophil survival may at least partly account for selective eosinophil recruitment to the asthmatic bronchial mucosa. The CC chemokines RANTES and monocyte chemotactic protein 3 (MCP-3) are potent eosinophil chemotactic factors, while the cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor (GM-CSF), and IL-3 prolong eosinophil survival. We have tested the hypothesis that elevated numbers of cells expressing mRNA for RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 are present in bronchial biopsies from atopic and nonatopic asthmatics compared with atopic and nonatopic nonasthmatic controls. The technique of in situ hybridization using 35S-labeled riboprobes was employed to detect mRNA+ bronchial mucosal cells. Compared with controls we observed significant increases in the numbers of cells expressing RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 (all P values < 0.001) in atopic and nonatopic asthmatics. These observations support the view that atopic and nonatopic asthma are associated with combined bronchial mucosal expression of CC chemokines (RANTES and MCP-3), together with eosinophil-active cytokines (IL-5, GM-CSF, and IL-3). These cytokines might contribute to the bronchial mucosal accumulation of activated eosinophils in both atopic and nonatopic variants of asthma.
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PMID:Bronchial mucosal expression of the genes encoding chemokines RANTES and MCP-3 in symptomatic atopic and nonatopic asthmatics: relationship to the eosinophil-active cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor, and IL-3. 899 72

Two novel human beta-chemokines, Ck beta-8 or myeloid progenitor inhibitory factor 1 (MPIF-1), and Ck beta-6 or MPIF-2, were discovered as part of a large scale cDNA sequencing effort. The MPIF-1 and MPIF-2 cDNAs were isolated from aortic endothelium and activated monocyte libraries, respectively. Both of the cDNAs were cloned into a baculovirus vector and expressed in insect cells. The mature recombinant MPIF-1 protein consists of 99 amino acids and is most homologous to macrophage inflammatory protein (MIP)-1alpha, showing 51% identity. It displays chemotactic activity on resting T lymphocytes and monocytes, a minimal but significant activity on neutrophils, and is negative on activated T lymphocytes. MPIF-1 is also a potent suppressor of bone marrow low proliferative potential colony-forming cells, a committed progenitor that gives rise to granulocyte and monocyte lineages. The mature recombinant MPIF-2 has 93 amino acid residues and shows 39 and 42% identity with monocyte chemoattractant protein (MCP)-3 and MIP-1alpha, respectively. It displays chemotactic activity on resting T lymphocytes, a minimal activity on neutrophils, and is negative on monocytes and activated T lymphocytes. On eosinophils, MPIF-2 produces a transient rise of cytosolic Ca2+ and uses the receptor for eotaxin and MCP-4. In hematopoietic assays, MPIF-2 strongly suppressed the colony formation by the high proliferative potential colony-forming cell (HPP-CFC), which represents a multipotential hematopoietic progenitor.
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PMID:Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors. 910 3

Macrophages were elicited by the subcutaneous implantation of ultra high molecular weight polyethylene (UHMWPE) for periods of 2, 7, and 14 days in rats. Exudates of varying volumes were produced that was comprised of granulocytes, monocytes, immature and mature macrophages, and T-lymphocytes. No B-lymphocytes were observed at any time periods. Cell types were identified by their granularity and positivity to the following antibodies: leucocyte common antigen (LCA, pan leucocyte); CD11b/c (macrophage/monocyte); CD5 (T-lymphocyte); CD45RA (B-lymphocyte); HIS48 (granulocyte); ED2 (mature macrophage); and MCP-1 (monocyte chemoattractant protein 1). Monocytes isolated from control rat blood demonstrated a size slightly larger than that of granulocytes but with less granularity. Their size and granularity were followed over increasing time periods. The macrophages elicited by UHMWPE showed a similar pattern, with the exception of an apparently highly granular subpopulation with volumes similar to that of granulocytes but significantly more granular. The granular macrophage subset had a very high degree of ED2 and MCP-1 positivity, and their proportion, compared with other macrophages, was greatest at 2 days. The high MCP-1 expression was accounted for by MCP-1 molecules bound to the surface of a small proportion of macrophages that were activated. It is postulated that this subpopulation was responsible for the synthesis of the MCP-1 and could indicate a mechanism by which monocytes are attracted to the site of an implanted material.
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PMID:Macrophage subpopulation differentiation by stimulation with biomaterials. 940 96

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

Interleukin (IL)-15 shares immuno-stimulatory properties with IL-2 and is a potent inducer of natural killer (NK) cell function. The major histocompatibility complex (MHC) class I-negative human small cell lung cancer (SCLC) cell line N592, engineered to express a modified IL-15 cDNA (N592/IL-15), secreted biologically active IL-15 (300-500 pg/ml), capable of boosting T-cell proliferation and NK activity 'in vitro'. The effect of IL-15 gene transfer on natural immunity 'in vivo' was assessed by xenotransplants in nude mice and compared with that of the IL-2 gene. N592 cells engineered with IL-2 (N592/IL-2) were promptly rejected, while N592/IL-15 displayed a significant delay in tumour growth and a slightly reduced take rate. However, in NK-depleted nude mice, N592/IL-15 displayed the same growth kinetics as unmodified N592 cells, and N592/IL-2 grew with slightly reduced kinetics. An impressive reactive cell infiltration, consisting mainly of macrophages and granulocytes, was associated with N592/IL-2 tumour rejection, while a more evident recruitment of NK cells was found in N592/IL-15 tumours. In both N592 transfected tumours, we found expression of chemoattractant molecules, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and monocyte chemoattractant protein (MCP)-1, while macrophage inflammatory protein (MIP)-2 was produced by endothelial cells only in N592/IL-2 tumours. In this tumour, very few and severely damaged microvessels were found, while microvessels were numerous in N592/IL-15 tumours. The potent recruitment of NK cells mediated by IL-15 gene transfer suggests its possible therapeutic use in tumours lacking MHC class I.
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PMID:Dissimilar anti-tumour reactions induced by tumour cells engineered with the interleukin-2 or interleukin-15 gene in nude mice. 1086 81

Examined were CCR2-deficient mice to clarify the contribution of macrophages via monocyte chemoattractant protein 1 (MCP-1 or CCL2)/CCR2 signaling to the pathogenesis of renal ischemia-reperfusion injury. Also evaluated was the therapeutic effects via the inhibition of MCP-1/CCR2 signaling with propagermanium (3-oxygermylpropionic acid polymer) and RS-504393. Renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. A large number of infiltrated cells and marked acute tubular necrosis in outer medulla after renal ischemia-reperfusion injury was observed. Ischemia-reperfusion induced the expression of MCP-1 mRNA and protein in injured kidneys, followed by CCR2-positive macrophages in interstitium in wild-type mice. The expression of MCP-1 was decreased in CCR2-deficient mice compared with wild-type mice. The number of interstitial infiltrated macrophages was markedly smaller in the CCR2-deficient mice after ischemia-reperfusion. CCR2-deficient mice decreased the number of interstitial inducible nitric oxide synthase-positive cells after ischemia-reperfusion. The area of tubular necrosis in CCR2-deficient mice was significantly lower than that of wild-type mice after ischemia-reperfusion. In addition, CCR2-deficient mice diminished KC, macrophage inflammatory protein 2, epithelial cell-derived neutrophil-activating peptide 78, and neutrophil-activating peptide 2 expression compared with wild-type mice accompanied with the reduction of interstitial granulocyte infiltration. Similarly, propagermanium and RS-504393 reduced the number of interstitial infiltrated cells and tubular necrosis up to 96 h after ischemia-reperfusion injury. These results revealed that MCP-1 via CCR2 signaling plays a key role in the pathogenesis of renal ischemia-reperfusion injury through infiltration and activation of macrophages, and it offers a therapeutic target for ischemia-reperfusion.
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PMID:CCR2 signaling contributes to ischemia-reperfusion injury in kidney. 1451 28

As an Old World nonhuman primate, baboons have been extensively used for research on dyslipidemia and atherogenesis. With increasing knowledge about the endothelium's role in the initiation and progression of atherosclerosis, the value of the baboon model can be increased by developing it for research on the role of dysfunctional endothelium in atherogenesis. Toward that goal, we have established and validated methods of isolating and culturing baboon femoral artery endothelial cells (BFAECs) and compared baboon endothelial cellular characteristics with those of humans. Our results indicated that baboon and human endothelial cells share similar growth and culture behaviors. As was the case for human endothelial cells, BFAECs responded to tumor necrosis factor (TNF)-alpha stimulation with increased expression of adhesion molecules (maximum increase for intracellular adhesion molecule (ICAM): 1.76 +/- 0.26-fold; vascular cell adhesion molecule (VCAM): 1.65 +/- 0.25-fold; E-selectin: 2.86 +/- 0.57-fold). However, BFAECs were hyporesponsive to lipopolysaccharide (LPS) (range, 0.25-20 microg/mL) in adhesion molecule expression, whereas 1 microg/mL LPS induced 2.14- to 3.71-fold increases in human endothelial cells. The differential responses to LPS were not related to TLR-2 and toll-like receptor (TLR)-4 expression on the cell surface. And baboon microvascular endothelial cells had similar features as BFAECs. We observed constitutive expression of interleukin (IL)-6, IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP)-1 in both human and baboon endothelial cells, and these cytokines were further induced by TNF-alpha and LPS. We also demonstrated that the responses to TNF-alpha or LPS varied among baboons maintained under the same dietary and environmental conditions, suggesting that response may be controlled by genetic factors.
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PMID:Comparative analysis of vascular endothelial cell activation by TNF-alpha and LPS in humans and baboons. 1521 Oct 29

In an in vitro whole blood model of artificial surface-induced inflammation, we have studied the contribution of leukocyte populations in the synthesis of inflammatory mediators. This was done by depleting the blood of specific cell types using magnetic beads coated with monoclonal antibodies against leukocyte surface antigens. Synthesis of interleukin 8 (IL-8) was highly dependent on CD15+ cells and was reduced by 80% when these cells were removed from the blood. Correspondingly, IL-8 production showed a high correlation with the concentration of granulocytes (r = 0.77, p < 0.0001). Synthesis of monocyte chemoattractant protein 1 (MCP-1) was dependent on CD14+ cells and was reduced by 35% when these cells were removed from the blood. Correspondingly, MCP-1 production correlated with the concentration of monocytes (r = 0.39, p < 0.0001). Synthesis of leukotriene B4 (LTB4) was highly dependent on CD15+ cells and was reduced by 75% when these cells were removed from the blood. Correspondingly, LTB4 production correlated strongly with the granulocyte concentration (r = 0.54, p < 0.0001). As expected, complement activation was not affected by cell depletion and did not correlate with the concentration of any of the cell types. Thus, artificial surface-induced IL-8 and LTB4 synthesis was almost exclusively granulocyte dependent. However, MCP-1 synthesis was mainly a product of monocytes, although granulocytes and other subpopulations may partly contribute. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005.
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PMID:Role of granulocytes and monocytes in the polyvinyl chloride-induced synthesis of interleukin 8, monocyte chemoattractant protein 1, and leukotriene B4. 1596 66

Seminal fluid is known to be responsible for orchestrating mating-induced immunomodulation. Central to this process are numerous cytokines that modulate uterine leukocyte recruitment and trafficking. Despite this, a comprehensive analysis of the cytokine profile of murine seminal fluid is lacking. This study addressed this issue by using multiplex immunoassays to characterise the profile of interleukin (IL)-1alpha , IL-1beta , IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha , MIP-1beta , regulated upon activation normal T-cell expressed and secreted (RANTES), and tumour necrosis factor (TNF)-alpha in fluid drawn from the seminal vesicles of single mice (n = 18). Their levels and ratios were compared with those found in serum. IL-1alpha , IL-1beta , IL-2, IL-5, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-17, GM-CSF, IFN-gamma, MCP-1 and TNF-alpha levels were significantly higher in serum; IL-4, G-CSF, eotaxin, KC and RANTES exhibited the opposite trend. Based on these findings, we propose a model of mating-induced immunomodulation that implicates seminal eotaxin, RANTES and MIP-1alpha in the relocation and concentration of extravasated migrating endometrial eosinophils to the luminal epithelium. Furthermore, KC may participate in uterine neutrophil chemotaxis and activation. Eotaxin and MIP-alpha , together with IL-1beta and IL-9, may also enhance further cytokine synthesis for endometrial antigen-presenting cell recruitment for processing paternal ejaculate antigens. IL-4 and G-CSF could also minimise deleterious cell-mediated immunity and modulate IFN-gamma production, thereby supporting the establishment of pregnancy.
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PMID:Multiplex determination of murine seminal fluid cytokine profiles. 1651 4

It has been suggested that monocytes/macrophages represent the pivotal cell type during early adaptive growth of pre-existent arterial anastomoses toward functional collateral arteries (arteriogenesis) upon arterial occlusion. This hypothesis was supported by previous studies providing evidence that elevation of the peripheral monocyte count, increased monocyte survival (e.g., granulocyte macrophage-colony stimulating factor), as well as enhanced attraction or adhesion (e.g., monocyte chemoattractant protein 1; intercellular adhesion molecule 1) of the latter cells correlates directly with the arteriogenic response to restore tissue perfusion. However, the experimental proof of the essential role of monocytes/macrophages remains to be given. We therefore hypothesized that arteriogenesis is reduced in a genuine, nonpharmocologically induced monocyte/macrophage-deficient model of femoral artery occlusion in osteopetrotic (op/op) mice. Total leukocyte count did not differ between op/op mice and control (B6C3Fe a/a-Csf1(+/+)) mice. op/op mice show a significant monocytopenia (0.67%+/-0.38% vs. 1.53%+/-0.32%), granulocytosis (33.66%+/-6.67% vs. 22.83+/-7.47%), and a concomitant, relative lymphopenia (65.67%+/-6.58% vs. 75.65%+/-7.31%). Microsphere-based perfusion measurement 7 days after femoral artery occlusion demonstrated a significantly reduced perfusion restoration upon femoral artery occlusion in op/op mice as compared with controls (28.19%+/-0.91% vs. 47.88%+/-2.49%). The application of a novel method of high resolution (microfocus X-ray system) angiography revealed a reduction of proliferation and diameter of collateral arteries. Quantitative immunohistology showed significantly lower numbers of macrophages in the surrounding tissue of proliferating arteries. This study provides additional evidence for the preeminent role of monocytes/macrophages during arteriogenesis in a genuine model of monocyte deficiency, i.e., without pharmacological intervention.
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PMID:Arteriogenesis depends on circulating monocytes and macrophage accumulation and is severely depressed in op/op mice. 1668 92


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