Circulating monocytes

NF-xB (Section 2.3.6). Additionally, patients with RA have increased concentrations of MCP-1 in their serum and synovial fluid when compared to patients with noninflammatory degenerative joint disease (Koch et al., 1992). Macrophages in the RA synovial lining constitu-tively express MCP-1, unlike normal circulating monocytes. 

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

Fig. 3. The role of FKN/CX3R1 in inducing atherosclerosis may involve two mechanisms. The first is the release of soluble FKN through cleavage of membrane-expressed FKN by TNF-alpha converting enzyme (TACE). Soluble FKN is then able to attract circulating monocytes and effector T cells expressing CX3CR1. The second mechanism is that of firm adhesion of circulating cells to membrane-bound FKN.

Rezaie-Majd A, Maca T, Bucek RA, et al. Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vase Biol 2002 22(7) 1194-1199. 

Cone RE, Chattopadhyay S, Sharafieh R, Li JC, O Rourke J, Goldschneider I Intracameral injection of antigen attracts circulating monocytic cells associated with anterior chamber-associated immune deviation to iris, blood and thymus. Association for Research in Vision and Ophthalmology, Annual Meeting, Fort Lauderdale, 2007, Abstr No 5208. 

As mentioned, Fukuda et al. (46) have recently shown that circulating monocytes count increased and reached its peak two days after human stent implantation (from 350 167 to 515 149/mm ). These data support the correlation between monocytes depletion and prevention of restenosis. Inactivation of systemic monocytes immediately after injury suppresses... 

Fukuda D, Shimada K, Tanaka A, Kawarabayashi T, Yoshiyama M, Yoshikawa J. Circulating monocytes and in-stent neointima after coronary stent implantation. J Am Coll Cardiol 2004 43 18-23. 

Recent evidence suggests that atherosclerosis is a chronic inflammatory process. The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Alterations of chemotactic and adhesive properties of the endothelium play an important role in this process [82]. Quercetin has been reported to inhibit the expression in glomerular cells of monocyte chemoattractant protein-1 (MCP-1) [83] a potent chemoattractant for circulating monocytes. Red wine reduced MCP-1 mRNA and protein expression in abdominal aorta of cholesterol fed rabbits after balloon injury and this effect was associated with a reduced neointimal hyperplasia [84]. The antioxidant-mediated inhibition of nuclear factor k B (NFkB) and the subsequent non selective reduction of cytokine transcription have been suggested to be responsible for these effects [83]. Additionally, quercetin downregulated both phorbol 12-myristate 13-acetate (PMA)- and tumour necrosis factor-a (TNFa)-induced intercellular adhesion molecule-1 (ICAM-1) expression in human endothelial cells [86]. 

Immunologic As discussed above, the most obvious immunologic effects in mice are the lymphohistiocytic infiltrates commonly observed in the parenchyma of numerous organs. These collections of histiocytes can sometimes be observed perivascularly and have been at times found in clusters, giving the appearance of microgranulomas. As would be expected, the increase in mononuclear cells in tissues is sometimes associated with increases in circulating monocytes, and plasma cytokine and chemokines concentrations. 

Circulating monocytes provide another major source of brain microglia (Bechmann et al., 2005, 2007). Perivascular microglial cells, which are bone marrow derived, continuously turn over in the CNS, and are immunoregulatory cells that connect the CNS with the peripheral immune system (Williams et al.,... 

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