Uptake of oxLDL and IL-10 Production by Macrophages Requires PAFR and CD36 Recruitment into the Same Lipid Rafts

Autor(es)

Rios, Francisco J. O. ^{[1, 2]} ; Ferracini, Matheus ^[1] ; Pecenin, Mateus ^[1] ; Koga, Marianna M. ^[1] ; Wang, Yajuan ^[3] ; Ketelhuth, Daniel F. J. ^[3] ; Jancar, S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Univ Glasgow, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark - Scotland

^[3] Karolinska Inst, Ctr Mol Med, Dept Med, Stockholm - Sweden

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 10 OCT 9 2013.
• Citações Web of Science: 16

Resumo

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 beta CD 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. (AU)

• Processo FAPESP: 06/03982-5 - Aspectos moleculares envolvidos na atividade microbicida e inflamatória de leucócitos no pulmão
• Beneficiário: Sônia Jancar
• Modalidade de apoio: Auxílio à Pesquisa - Temático