title: Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts.
abstract: Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil ; BHF-Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Francisco J O
authors.initials: FJ
authors.lastname: Rios
authors.forename: Matheus
authors.initials: M
authors.lastname: Ferracini
authors.forename: Mateus
authors.initials: M
authors.lastname: Pecenin
authors.forename: Marianna M
authors.initials: MM
authors.lastname: Koga
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Daniel F J
authors.initials: DF
authors.lastname: Ketelhuth
authors.forename: S
authors.initials: S
authors.lastname: Jancar
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C106354:flotillins; C099252:oxidized low density lipoprotein; C039351:platelet activating factor receptor; D016753:Interleukin-10; D005677:G(M1) Ganglioside