In CCR2-/- mice monocyte recruitment and egress of LDL cholesterol in vivo is impaired.
Recruitment of macrophages plays an important role in initiation of atheroma, but their involvement in cholesterol clearance during regression is unknown. We developed a mouse model to quantitate cholesterol clearance from a depot of cationized LDL injected into a leg muscle, which evokes a sterile inflammatory reaction. In the CCR2(-/-) mice, cholesterol clearance was significantly slower than in C57BL controls because of decrease in cholesteryl ester (CE) hydrolysis, which is mandatory prior to cholesterol efflux. In CCR2(-/-) mice, macrophage recruitment to the injected site, identified by immunohistochemistry, was markedly delayed. CE hydrolysis was also significantly reduced in thioglycollate elicited peritoneal exudate cells of CCR2(-/-) mice, related to paucity of macrophages in the cell differential. The present study provides definite evidence that recruitment of macrophages is required for LDL cholesterol clearance, which plays a prominent role in regression of an atheroma.
Stein
Olga
O
Department of Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Dabach
Yedida
Y
Ben-Naim
Mazal
M
Halperin
Gideon
G
Charo
Israel F
IF
Stein
Yechezkiel
Y
D000818:Animals; D001692:Biological Transport; D002465:Cell Movement; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*
C515335:Ccr2 protein, mouse; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008055:Lipids; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D002784:Cholesterol