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CCL5 Promotes Macrophage Recruitment and Survival in Human Adipose Tissue

INSERM U872, team 7, Nutriomique, 15, rue de l'école de médecine, 75006, Paris, France.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 5.53). 11/2009; 30(1):39-45. DOI: 10.1161/ATVBAHA.109.197442
Source: PubMed

ABSTRACT To examine the role of adipose-produced chemokine, chemokine ligand (CCL) 5, on the recruitment and survival of macrophages in human white adipose tissue (WAT).
CCL5 levels measured by enzyme immunoassay in serum and by real-time polymerase chain reaction in WAT were higher in obese compared to lean subjects. CCL5, but not CCL2, secretion was higher in visceral compared to subcutaneous WAT. CCL5 mRNA expression was positively correlated with the inflammatory macrophage markers as CD11b, tumor necrosis factor-alpha, and IL-6 in visceral WAT (n=24 obese subjects), and was higher in macrophages than other WAT cells. We found that CCL5 triggered adhesion and transmigration of blood monocytes to/through endothelial cells of human WAT. Whereas in obese WAT apoptotic macrophages were located around necrotic adipocytes, we demonstrated that CCL5, but not CCL2, protected macrophages from free cholesterol-induced apoptosis via activation of the Akt/Erk pathways.
CCL5 could participate in the inflammation of obese WAT by recruiting blood monocytes and exerting antiapoptotic properties on WAT macrophages. This specific role of CCL5 on macrophage survival with maintenance of their lipid scavenging function should be taken into account for future therapeutic strategies in obesity-related diseases.

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    • "Regulated upon Activation Normal T cells Expressed and Secreted (RANTES or CCL5) is a powerful proinflammatory mediator of the CC chemokine family that regulates the mobilization and, in certain cases, promotes survival of immune inflammatory cells from the bloodstream into tissues and other areas of injury and infection [3] [8] [9]. Although the chemotactic activity of RANTES on immune cells to injured and infected areas is beneficial, sustained production of RANTES is associated with several detrimental effects such as atherosclerosis [10] [11], arthritis rheumatoid [12], liver disease [13] [14], and viral infection [15] that share in common chronic inflammatory response. "
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    • "Conversely, these effects are reduced with deficiency in CCL2 (Kanda et al., 2006). A recent report has shown that the chemokine, CCL5 (also known as RANTES), participates in WAT macrophage recruitment in obese humans (Keophiphath et al., 2010). Although deficiency or antagonism of chemokines has shown to lessen obesity-induced macrophage infiltration, accumulation of macrophages is not completely abolished, suggesting that non-chemokine factors may play a role in recruitment during obesity. "