Individual variation of scavenger receptor expression in human macrophages with oxidized low-density lipoprotein is associated with a differential inflammatory response.
Atherosclerosis is an inflammatory disease in which oxidized low-density lipoprotein (oxLDL) plays important roles. Scavenger receptors (SR) CD36, SR-A, and LOX-1 uptake over 90% of the oxLDL leading to foam cell formation and secretion of inflammatory cytokines. To investigate whether the interindividual differences in macrophage SR gene expression could determine the inflammatory variability in response to oxLDL, we quantified the gene and protein expression of SR and inflammatory molecules from macrophages isolated from 18 volunteer subjects and incubated with oxLDL for 1, 3, 6, and 18 h. The individual gene expression profile of the studied SR at 1 h of incubation was highly variable, showing a wide fold-change range: CD36: -3.57-4.22, SR-A: -5.0-4.43, and LOX-1: -1.56-75.32. We identified subjects as high and low responders depending on whether their SR gene expression was above or below the median, showing a different inflammation response pattern. CD36 and LOX-1 gene expression correlated positively with IL-1beta; SR-A correlated negatively with IL-8 and positively with PPARgamma and NF-kappaBIotaA. These results were confirmed in the same subjects 3 mo after the first sampling. Furthermore, a negative correlation existed between CD36 and SR-A at protein level after 18 h of oxLDL incubation (R = -0.926, p = 0.024). These data would suggest that the type of SR could determine the macrophage activation: more proinflammatory when associated to CD36 and LOX-1 than when associated with SR-A.
Martín-Fuentes
Paula
P
Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud, Paseo Isabel la Católica 103, 50009 Zaragoza, Spain. pmartin.iacs@aragon.es
Civeira
Fernando
F
Recalde
Delia
D
García-Otín
Angel Luis
AL
Jarauta
Estíbaliz
E
Marzo
Isabel
I
Cenarro
Ana
A
D000328:Adult; D018955:CD36 Antigens / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000494:pharmacology* / Q000502:physiology; D008262:Macrophage Activation / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D051116:Receptors, Scavenger / Q000235:genetics* / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism
D018955:CD36 Antigens; D016207:Cytokines; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein