title: In CCR2-/- mice monocyte recruitment and egress of LDL cholesterol in vivo is impaired.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Stein
authors.forename: Yedida
authors.initials: Y
authors.lastname: Dabach
authors.forename: Mazal
authors.initials: M
authors.lastname: Ben-Naim
authors.forename: Gideon
authors.initials: G
authors.lastname: Halperin
authors.forename: Israel F
authors.initials: IF
authors.lastname: Charo
authors.forename: Yechezkiel
authors.initials: Y
authors.lastname: Stein
mesh_terms: 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*
chemical_list: C515335:Ccr2 protein, mouse; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008055:Lipids; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D002784:Cholesterol