title: Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice.
abstract: Reverse cholesterol transport (RCT) pathway from macrophage foam cells initiates when HDL particles cross the endothelium, enter the interstitial fluid, and induce cholesterol efflux from these cells. We injected [(3)H]cholesterol-loaded J774 macrophages into the dorsal skin of mice and measured the transfer of macrophage-derived [(3)H]cholesterol to feces [macrophage-RCT (m-RCT)]. Injection of histamine to the macrophage injection site increased locally vascular permeability, enhanced influx of intravenously administered HDL, and stimulated m-RCT from the histamine-treated site. The stimulatory effect of histamine on m-RCT was abolished by prior administration of histamine H1 receptor (H1R) antagonist pyrilamine, indicating that the histamine effect was H1R-dependent. Subcutaneous administration of two other vasoactive mediators, serotonin or bradykinin, and activation of skin mast cells to secrete histamine and other vasoactive compounds also stimulated m-RCT. None of the studied vasoactive mediators affected serum HDL levels or the cholesterol-releasing ability of J774 macrophages in culture, indicating that acceleration of m-RCT was solely due to increased availability of cholesterol acceptors in skin. We conclude that disruption of the endothelial barrier by vasoactive compounds enhances the passage of HDL into interstitial fluid and increases the rate of RCT from peripheral macrophage foam cells, which reveals a novel tissue cholesterol-regulating function of these compounds.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kareinen
authors.affiliation: IIB Sant Pau, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona-CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain.
authors.forename: Lídia
authors.initials: L
authors.lastname: Cedó
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Reija
authors.initials: R
authors.lastname: Silvennoinen
authors.affiliation: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Pirkka-Pekka
authors.initials: PP
authors.lastname: Laurila
authors.affiliation: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: IIB Sant Pau, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona-CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.affiliation: IIB Sant Pau, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona-CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
authors.affiliation: IIB Sant Pau, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona-CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain.
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escola-Gil
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee-Rueckert
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001920:Bradykinin / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D005487:Foam Cells / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D008076:Cholesterol, HDL; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D006632:Histamine; D002784:Cholesterol; D001920:Bradykinin
keywords: bradykinin; cholesterol; foam cells; high density lipoprotein; histamine; lipoproteins; mast cells; serotonin