Disease relevance of MCP-1

• CONCLUSION: We conclude that latent adenoviral infection inhibits the anti-inflammatory effects of glucocorticoids on allergen-induced eotaxin and MCP-1 expression through AP-1, leading to steroid-resistant allergic lung inflammation [1].
• A very close cell-to-cell correlation between MCP-1 and porcine circovirus 2 was seen in serial sections of lymph nodes [2].
• Monocyte chemoattractant protein-1 (MCP-1) but not interleukin-8 (IL-8) was detected by in situ hybridization using a nonradioactive digoxigenin-labeled complementary DNA probe in granulomatous lesions of lymph nodes from 20 pigs with naturally occurring postweaning multisystemic wasting syndrome (PMWS) [2].
• MCP-1 and TGF-beta were significantly higher in heart and lung and IL-6R increased in heart after brain death (P < 0.05) [3].
• It was recently found that propagermanium, which is clinically used for the treatment of chronic hepatitis type B in Japan, markedly suppresses monocyte chemotaxis in response to macrophage chemoattractant protein-1 (MCP-1) through inhibition of its receptor, C-C chemokine receptor 2, in vitro [4].

High impact information on MCP-1

• We found that two CCAAT/enhancer binding protein (C/EBP) binding sites located between 2.6 and 3.6 kb upstream of the MCP-1 gene were responsible for the induction by p110CAAX [5].
• Guinea pig MCP-1 attracted about 34% of input human monocytes at 5 x 10(-9) M [6].
• These results suggest that monocytes lose responsiveness to MCP-1 after differentiating to macrophages [6].
• Recombinant guinea pig MCP-1 was expressed in COS-7 cells, then purified by a three step procedure with orange A-agarose, carboxymethyl-HPLC, and reversed phase-HPLC [6].
• Conditioned medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic endothelial cells (PAEC) to assess proliferation [7].

Biological context of MCP-1

• Early downregulation of MCP-1 could attenuate the inflammation within the vascular wall and prevent the development of atherosclerotic lesions [8].
• Using this setting, the dose application of 300 microg MCP-1 plasmid DNA (the maximal dose tested) demonstrated the highest MCP-1 expression signal [9].
• We therefore assume that pMCP5 encodes the amino acid sequence for porcine MCP-1 [10].
• The cDNA insert was 742 bp long, with an open reading frame (ORF) encoding a protein of 99 amino acid residues which by comparison with known amino acid sequences of MCPs yielded highest identities with MCP-1 sequences [10].
• In vivo human MCP-1 transfection in porcine arteries by intravascular electroporation [9].

Anatomical context of MCP-1

• Human MCP-1 attracted 1% of input guinea pig peritoneal exudate macrophages at its highest concentration of 2.5 x 10(-8) M [6].
• The bacterial cell wall was observed to be the major cytokine-inducting components, whereas capsule expression was important for MCP-1 activation [11].
• Real-time PCR analysis revealed that pre-treatment of neutrophils induced elevated levels of IL-8 and TNF-alpha mRNA and protein as well as superoxide, but not mRNA for MCP-1, IFN-gamma, or TGF-beta when compared to neutrophils pre-stimulated with media alone [12].
• We also defined, in vitro, whether bone marrow (BM) cells secrete vascular endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP-1) [7].
• Collateralization in a porcine hindlimb model served to provide a proof-of-principle for the functional benefit of MCP-1 overexpression [13].

Associations of MCP-1 with chemical compounds

• Owing to clinical disadvantages of protein infusion, a nonviral, liposome-based MCP-1 gene transfer was developed [13].
• The individual and combined effects of inhaled nitric oxide (NO) and hyperoxia on lung MCP-1 and CCR-2 in relation to lung leukocyte dynamics are unknown [14].
• It was first confirmed that propagermanium inhibited the migration of porcine monocytes in response to MCP-1 at therapeutic concentrations in vitro [4].
• The passage of THP-1 cells through the coculture was stimulated by MCP-1 and LPC [15].
• The effects of wine consumption on intimal response and monocyte chemotactic protein-1 (MCP-1) expression were studied in cholesterol-fed rabbits [16].

Other interactions of MCP-1

• We verified the expression of mRNAs encoding the cytokines IL-1alpha, -6, -7, -8, -18, TNF-alpha and GM-CSF, but not TGF-beta or MCP-1 [17].
• There was little or no positive staining for CRP, SRA, or MCP-1 in the RCA of NF pigs, but there was extensive staining in lipidladen macrophage foam cells in the HF pigs [18].
• Eotaxin, monocyte chemoattractant protein 1 (MCP-1), and RANTES expression in the lung were analyzed by means of Northern blotting, and the binding activity of activator protein 1 (AP-1) and nuclear factor kappaB in nuclear extracts from the lung was analyzed with electrophoretic mobility shift assays [1].
• Additionally, the mRNA expression for IL-6R, ICAM-1, MCP-1, and TGF-beta was determined in each organ [3].
• RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner [7].

Analytical, diagnostic and therapeutic context of MCP-1

• At the time of occlusion, MCP-1 and control DNA/DC-30 lipoplexes were transferred to femoral arteries of Goettingen minipigs (two therapeutic MCP-1 groups: 2 and 4 microg and one control group), using the Infiltrator local drug-delivery device [13].
• A second group of animals was evaluated after intra-arterial infusion of 2.0 microg/h of MCP-1 for 48 h (followed by 12 days of PBS; n = 13) or 2 wk continuously (n = 12) [19].
• Modulation of collateral artery growth in a porcine hindlimb ligation model using MCP-1 [19].
• Modulation of the process of arteriogenesis is feasible in this large animal model via intra-arterial infusion of the Cys-Cys-chemokine MCP-1 [19].
• RT PCR employing poly(A+)RNA from porcine luteal cells and a combination of primers designed from the known bovine MCP-1 cDNA identified the luteal cells as a source of MCP-1 [10].

References