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Individual Variation of Scavenger Receptor Expression in Human Macrophages with Oxidized Low-Density Lipoprotein Is Associated with a Differential Inflammatory Response¹

Paula Martín-Fuentes^2,*, Fernando Civeira^*, Delia Recalde^*, Angel Luis García-Otín^*, Estíbaliz Jarauta^*, Isabel Marzo and Ana Cenarro^*

^* Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain; and Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain

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-1β; SR-A correlated negatively with IL-8 and positively with PPAR and NF-BIA. 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Fondo de Investigaciones Sanitarias (FIS PI031106) and Ministerio de Educación y Ciencia (SAF2005/07042).

² Address correspondence and reprint requests to Dr. Paula Martín-Fuentes, Laboratorio de Investigación Molecular, Hospital Universitario Miguel Server, Paseo Isabel la Católica, 1-3, 50009 Zaragoza, Spain. E-mail address: pmartin.iacs{at}aragon.es

³ Abbreviations used in this paper: LDL, low-density lipoprotein; oxLDL, oxidized LDL; SR, scavenger receptor; MFI, mean fluorescence intensity; RFU, relative fluorescence unit; CRP, C-reactive protein; TPS, tryptase.

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