363 Original Paper Cell Physiol Biochem 2011;27:363-372 Accepted: March 09, 2011 Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology and Biochemistr and Biochemistr and Biochemistr and Biochemistr and Biochemistry Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2011 S. Karger AG, Basel 1015-8987/11/0274-0363$38.00/0 Accessible online at: www.karger.com/cpb Pivotal Role for Platelet-Activating Factor Receptor in CD36 Expression and oxLDL Uptake by Human Monocytes/Macrophages Francisco J.O. Rios, Magnus Gidlund and Sonia Jancar Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil Sonia Jancar Department of Immunology, Institute of Biomedical Sciences University of Sao Paulo, Av. Prof. Lineu Prestes, 1730, ICB IV - Sala 140/146, 05508-900 Sao Paulo (Brazil) E-Mail sojancar@icb.usp.br Key Words OxLDL  Macrophages  CD36  Platelet-Activating Factor Receptor  Foam cells  Atherosclerosis Copyright © 2011 S. Karger AG, Basel Abstract The uptake of oxLDL by CD36 is not regulated by intracellular levels of cholesterol, leading to macro- phage differentiation into foam cells which play a major role in atherosclerosis. Furthermore, oxLDL competes with PAF in macrophages for binding to PAF receptors (PAFR). Here we investigated the involvement of PAFR in CD36 expression and uptake of oxLDL by human monocytes/macrophages. Adherent peripheral blood mononuclear cells were treated with PAFR-an- tagonists (WEB2170, CV3988); inhibitors of ERK1/2 (PD98059), p38 (SB203580), JNK (SP600125) or diluents, before stimulation with oxLDL or PAF. After 24 h, uptake of FITC–oxLDL and expression of CD36 was determined by flow cytometry and phosphoryla- tion of MAP-kinases by Western blot. It was shown that the uptake of oxLDL was reduced by PAFR antagonists. CD36 expression was up-regulated by oxLDL, an effect reversed by PAFR antagonists. The up-regulation of CD36 and oxLDL uptake both required MAP-kinases activation. The oxLDL–induced ERK1/2 and JNK but not p38 phosphorylation was reversed by PAFR-antagonists suggesting that oxLDL signalling involves PAFR dependent and independent pathways. In macrophages from PAFR -/- mice, oxLDL was unable to up-regulate CD36 expression and the oxLDL uptake was reduced compared to wild type. These results suggest that oxLDL interacts with PAFR in macrophages to increase CD36 expression and oxLDL uptake. Whereas pharmacological intervention at the level of PAFR would be beneficial in atherosclerosis remains to be determined. Introduction CD36 is a class B scavenger receptor expressed mainly on the membranes of monocytes/macrophages, platelets and adipocytes. It was first identified as a thrombospondin-1 receptor, but it is now known that this receptor is able to interact with different and