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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    ABSTRACT: RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fifty-seven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated. There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (P < 0.05). Physical exercise significantly reduced the expression of both RANTES and CCR5 (P < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNF- α , IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1ra (P = 0.001) and positively with proinflammatory IP-10 and TBARS levels (P < 0.05). Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue.
    Mediators of Inflammation 04/2014; 2014. DOI:10.1155/2014/627150 · 2.42 Impact Factor
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    • "that CXCL14 might also be involved during homeostatic LC turnover (Ginhoux et al., 2006; Keophiphath et al., 2010; Schaerli et al., 2005). The constitutive chemokine CXCL14 has also been shown to be a potent chemo-attractant for CD14 + -LC progenitors. "
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    ABSTRACT: Epidermal Langerhans cells (LC) play a key role in initiation and regulation of immune responses. Whereas LC migration out of the epidermis upon environmental assault is extensively studied, the mechanisms involved in the (re)population of the epidermis with LC are poorly understood. Here, we investigated the immigration of LC derived from the human MUTZ-3 cell line (MUTZ-LC) into the epidermis of a full thickness skin equivalent, comprising a fully differentiated epidermis on a fibroblast-populated dermis. MUTZ-LC were used to determine which epidermis-derived chemokines play a role in mediating LC trans-dermal migration into the epidermis. We found evidence for a role of keratinocyte-derived CCL5 and CCL20 in the chemo-attraction of MUTZ-LC. Neutralizing antibodies against CCL5 and CCL20 blocked LC migration towards keratinocytes. Secretion of these two chemokines was associated with incorporation of MUTZ-LC into the epidermis of full thickness skin equivalents. In conclusion, our findings suggest that epidermis derived CCL5 and CCL20 are pivotal mediators in recruitment of LC into the epidermis.
    European journal of cell biology 08/2012; 91(10):765-73. DOI:10.1016/j.ejcb.2012.06.004 · 3.70 Impact Factor
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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. "