CCL5 promotes macrophage recruitment and survival in human adipose tissue.
OBJECTIVE
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).


RESULTS
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.


CONCLUSIONS
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.
Keophiphath
Mayoura
M
INSERM U872, team 7, Nutriomique, 15, rue de l'école de médecine, 75006, Paris, France.
Rouault
Christine
C
Divoux
Adeline
A
Clément
Karine
K
Lacasa
Danièle
D
D052436:Adipose Tissue, White / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D001706:Biopsy; D001835:Body Weight / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D018946:Chemokine CCL5 / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009767:Obesity, Morbid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C483024:CCL5 protein, human; D039481:CD11b Antigen; D018946:Chemokine CCL5; C508600:IL6 protein, human; C509295:ITGAM protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha