title: Human scavenger protein AIM increases foam cell formation and CD36-mediated oxLDL uptake.
abstract: AIM is expressed by macrophages in response to agonists of the nuclear receptors LXR/RXR. In mice, it acts as an atherogenic factor by protecting macrophages from the apoptotic effects of oxidized lipids. In humans, it is detected in atherosclerotic lesions, but no role related to atherosclerosis has been reported. This study aimed to investigate whether the role of hAIM extends beyond inhibiting oxidized lipid-induced apoptosis. To accomplish this goal, functional analysis with human monocytic THP1 cells and macrophages differentiated from peripheral blood monocytes were performed. It was found that hAIM reduced oxLDL-induced macrophage apoptosis and increased macrophage adhesion to endothelial ICAM-1 by enhancing LFA-1 expression. Furthermore, hAIM increased foam cell formation, as shown by Oil Red O and Nile Red staining, as well as quantification of cholesterol content. This was not a result of decreased reverse cholesterol transport, as hAIM did not affect the efflux significantly from [(3)H] Cholesterol-laden macrophages driven by plasma, apoA-I, or HDL2 acceptors. Rather, flow cytometry studies indicated that hAIM increased macrophage endocytosis of fluorescent oxLDL, which correlated with an increase in the expression of the oxLDLR CD36. Moreover, hAIM bound to oxLDL in ELISA and enhanced the capacity of HEK-293 cells expressing CD36 to endocytose oxLDL, as studied using immunofluorescence microscopy, suggesting that hAIM serves to facilitate CD36-mediated uptake of oxLDL. Our data represent the first evidence that hAIM is involved in macrophage survival, adhesion, and foam cell formation and suggest a significant contribution to atherosclerosis-related mechanisms in the macrophage.
authors.affiliation: 1.Ctra Can Ruti, camí de les escoles s/n, Edifici de Recerca, Planta 1, 08916 Badalona, Spain. mrsarrias@igtp.cat; Twitter: http://www.twitter.com/mrsarrias.
authors.forename: Núria
authors.initials: N
authors.lastname: Amézaga
authors.forename: Lucía
authors.initials: L
authors.lastname: Sanjurjo
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.forename: Gemma
authors.initials: G
authors.lastname: Aran
authors.forename: Begoña
authors.initials: B
authors.lastname: Pérez-Cabezas
authors.forename: Patricia
authors.initials: P
authors.lastname: Bastos-Amador
authors.forename: Carolina
authors.initials: C
authors.lastname: Armengol
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilella
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escolà-Gil
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
authors.forename: Francesc E
authors.initials: FE
authors.lastname: Borràs
authors.forename: Annabel F
authors.initials: AF
authors.lastname: Valledor
authors.forename: Maria-Rosa
authors.initials: MR
authors.lastname: Sarrias
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D004705:Endocytosis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005487:Foam Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018955:CD36 Antigens; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL; D000099192:CD69 Antigens; C099252:oxidized low density lipoprotein
keywords: CD5L; Spα; apoptosis; atherosclerosis; macrophage