Randolph, G. J. Emigration of monocyte-derived cells to lymph nodes during resolution of inflammation and its failure in atherosclerosis. Curr. Opin. Lipidol. 19, 462-468

Department of Gene and Cell Medicine, and the Immunology Institute, 1425 Madison Avenue, Mount Sinai School of Medicine, New York 10029, USA.
Current Opinion in Lipidology (Impact Factor: 5.8). 11/2008; 19(5):462-8. DOI: 10.1097/MOL.0b013e32830d5f09
Source: PubMed

ABSTRACT This review compares the fate of monocyte-derived cells that enter atherosclerotic plaques with those that accumulate at other sites of inflammation.
Resolution of inflammatory reactions involves emigration of monocyte-derived cells out of the inflamed site through nearby lymphatic vessels. However, this emigratory process associated with resolution is impaired in atherosclerosis. The mechanism for impeded emigration from plaques in vivo remains to be determined, but multiple factors are likely involved, including specialized properties of artery walls and a negative impact of lipid mediators on monocyte-derived cell migration.
Impaired egress would be expected to compound macrophage accumulation within plaques, contribute to build-up of necrotic pools, and explain in part the reticence of many plaques to regress, or resolve. Restoration of the capacity of monocyte-derived cells to leave plaques would, by contrast, be expected to facilitate regression, but it remains to be determined whether restoring egress may sometimes provoke unwanted outcomes as well.

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Available from: Gwendalyn J Randolph, May 09, 2014
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    • "Several processes contribute to the progressive accumulation of leukocytes in the atherosclerotic plaque, the most obvious, and supra mentioned, being leukocyte recruitment [7] [10] [13] [14]. However macrophage survival [15] and proliferation [16] [17] in the plaque as well as the limited ability of leukocytes to leave atherosclerotic lesions [18] represent important processes critically controlling the number of macrophages within atherosclerotic lesions (Fig. 1a). "
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    ABSTRACT: Atherosclerosis is commonly looked upon as a chronic inflammatory disease of the arterial wall arising from an unbalanced lipid metabolism and a maladaptive inflammatory response. However, atherosclerosis is not merely an inflammation of the vessel wall. In fact, the cardinal signs of unstable atherosclerotic lesions are primarily characteristics of failed resolution of a chronic inflammation. In contrast to acute inflammatory events which are typically self-limiting, atherosclerosis is an unresolved inflammatory condition, lacking the switch from the pro-inflammatory to the pro-resolving phase, the latter characterized by termination of inflammatory cell recruitment, removal of inflammatory cells from the site of inflammation by apoptosis and dead cell clearance, reprogramming of macrophages toward an anti-inflammatory, regenerative phenotype, and finally egress of effector cells and tissue regeneration. Here we present an overview on mechanisms of failed resolution contributing to atheroprogression and deliver a summary of novel therapeutic strategies to restore resolution in inflamed arteries. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Seminars in Immunology 04/2015; DOI:10.1016/j.smim.2015.03.013 · 6.12 Impact Factor
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    • "Recruited monocytes/macrophages may emigrate from vessels and enter lymph nodes, which are associated with regression of atherosclerotic lesions [21]. Notably, CD62L (L-selectin) expressed by leukocytes, including Ly6C+ monocytes, is important for circulation to lymph nodes through high endothelial venules (HEV) [15]. "
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    ABSTRACT: Monocytes express various receptors, which monitor and sense environmental changes. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. Monocytes can differentiate into inflammatory or anti-inflammatory subsets. Upon tissue damage or infection, monocytes are rapidly recruited to the tissue, where they can differentiate into tissue macrophages or dendritic cells. Given the rapid progress in monocyte research from broad spectrum of inflammatory diseases, there is a need to summarize our knowledge in monocyte heterogeneity and its impact in human disease. In this review, we describe the current understanding of heterogeneity of human and murine monocytes, the function of distinct subsets of monocytes, and a potential mechanism for monocyte differentiation. We emphasize that inflammatory monocyte subsets are valuable biomarkers for inflammatory diseases, including cardiovascular diseases.
    01/2014; 2(1):1. DOI:10.1186/2050-7771-2-1
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    • "This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. EMBO Mol Med (2013) 5, 1901–1917 material, in an atherosclerotic plaque the loading of oxLDL into macrophages shifts them to a more sessile, foam‐cell phenotype, and these foam cells do not leave the lesion after clearing the lipids (Angeli et al, 2004; Randolph, 2008). The trapping of cholesterol‐engorged foam cells causes the plaque to expand through the recruitment of additional leukocytes and vascular smooth muscle cells (VSMCs). "
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    EMBO Molecular Medicine 12/2013; 5(12). DOI:10.1002/emmm.201302842 · 8.25 Impact Factor
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