Oxidized LDL induces alternative macrophage phenotype through activation of CD36 and PAFR.
OxLDL is recognized by macrophage scavenger receptors, including CD36; we have recently found that Platelet-Activating Factor Receptor (PAFR) is also involved. Since PAFR in macrophages is associated with suppressor function, we examined the effect of oxLDL on macrophage phenotype. It was found that the presence of oxLDL during macrophage differentiation induced high mRNA levels to IL-10, mannose receptor, PPAR γ and arginase-1 and low levels of IL-12 and iNOS. When human THP-1 macrophages were pre-treated with oxLDL then stimulated with LPS, the production of IL-10 and TGF- β significantly increased, whereas that of IL-6 and IL-8 decreased. In murine TG-elicited macrophages, this protocol significantly reduced NO, iNOS and COX2 expression. Thus, oxLDL induced macrophage differentiation and activation towards the alternatively activated M2-phenotype. In murine macrophages, oxLDL induced TGF- β , arginase-1 and IL-10 mRNA expression, which were significantly reduced by pre-treatment with PAFR antagonists (WEB and CV) or with antibodies to CD36. The mRNA expression of IL-12, RANTES and CXCL2 were not affected. We showed that this profile of macrophage activation is dependent on the engagement of both CD36 and PAFR. We conclude that oxLDL induces alternative macrophage activation by mechanisms involving CD36 and PAFR.
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Avenida Professor Lineu Prestes 1730, ICB IV-Sala 140/146, 05508-900 Sao Paulo, SP, Brazil. fjorios@usp.br
Francisco J
FJ
Rios
Marianna M
MM
Koga
Mateus
M
Pecenin
Matheus
M
Ferracini
Magnus
M
Gidlund
S
S
Jancar
D000818:Animals; D001119:Arginase / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D009569:Nitric Oxide / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
D018955:CD36 Antigens; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D047495:PPAR gamma; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C099252:oxidized low density lipoprotein; C039351:platelet activating factor receptor; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D001119:Arginase