The role of TLR2, TLR4 and CD36 in macrophage activation and foam cell formation in response to oxLDL in humans.
Toll-like receptor (TLR)2, TLR4 and CD36 are central in inflammation and the development of atherosclerosis. Oxidized low-density lipoprotein (oxLDL) plays a critical role in this disease through its involvement in the formation of foam cells and the activation of leukocytes. The aim of this research was to analyze the role of TLR2, TLR4 and CD36 in foam cell differentiation and macrophage activation.


METHODS
Human macrophages were incubated with monoclonal antibodies specific for TLR2, TLR4 and CD36 prior to stimulation with oxLDL. Subsequently, we analyzed foam cell formation, cytokine secretion, histocompatibility complex (MHC) class II molecules and CD86 expression and T cell proliferation.


RESULTS
The stimulation of macrophages with oxLDL induced foam cell formation, cytokine secretion, HLA-DR and CD86 expression and T cell proliferation. The blockage of TLR2, TLR4 and CD36 reduced the secretion of IL-1β, IL-6 and IL-8, the expression of HLA-DR and CD86, T cell proliferation and foam cell formation. However, the blockage of TLR2 did not affect the formation of foam cells.


CONCLUSIONS
Our study demonstrates that TLR2, TLR4 and CD36 participate in the immune response to oxLDL by inducing an increase in pro-inflammatory cytokines, the expression HLA-DR and CD86 and the proliferation of T cells. However, TLR2 does not participate in the formation of foam cells, while TLR4 and CD36 play a relevant role in this process. These findings suggest that the activation of these receptors by oxLDL contributes to the pathogenesis of atherosclerosis.
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico.
Luis
L
Chávez-Sánchez
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico; Departamento de Inmunología, ENCB, IPN, México D.F., Mexico.
Montserrat Guadalupe
MG
Garza-Reyes
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico.
José Esteban
JE
Espinosa-Luna
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico.
Karina
K
Chávez-Rueda
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico.
María Victoria
MV
Legorreta-Haquet
Unidad de Investigación Médica en Inmunología, UMAE, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS, México D.F., Mexico. Electronic address: fblanco1@terra.com.mx.
Francisco
F
Blanco-Favela
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D051940:B7-2 Antigen / Q000378:metabolism; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005487:Foam Cells; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D051940:B7-2 Antigen; D018955:CD36 Antigens; D016207:Cytokines; D006684:HLA-DR Antigens; D008077:Lipoproteins, LDL; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein