Abstract
BackgroundMacrophages play a proatherosclerotic role in atherosclerosis via oxLDL uptake. As an adhesion molecular of I-type lectins, Siglec-1 is highly expressed on circulating monocytes and plaque macrophages of atherosclerotic patients, but the exact role of Siglec-1 has not been elucidated.MethodsIn this study, oxLDL was used to stimulate Siglec-1 and some oxLDL receptors (SR-BI, CD64, CD32B, LOX-1 and TLR-4) expression on bone marrow-derived macrophages, whereas small interfering RNA was used to down-regulate Siglec-1. Meanwhile, an ELISA-based assay for Siglec-1-oxLDL interaction was performed, and co-immunoprecipitation (co-IP) and laser scanning confocal microscopy (LSCM) were used to determine the role of Siglec-1 in oxLDL uptake by macrophages.ResultsWe found that oxLDL could up-regulate the expression of various potential oxLDL receptors, including Siglec-1, in a dose-dependent manner. Moreover, down-regulation of Siglec-1 could attenuate oxLDL uptake by Oil red O staining. LSCM revealed that Siglec-1 and CD64/SR-BI may colocalize on oxLDL-stimulated macrophage surface, whereas co-IP showed that Siglec-1 and SR-BI can be immunoprecipitated by each other. However, no direct interaction between Siglec-1 and oxLDL was found in the in vitro protein interaction system.ConclusionsThus, Siglec-1 can interact with SR-BI in the phagocytosis of oxLDL by macrophages, rather than act as an independent receptor for oxLDL.
Highlights
Reduction of plasma level of oxidized LDL may have a protective role in the initiation and progression of atherosclerosis (AS)
Siglec-1 can interact with scavenger receptor (SR)-BI in the phagocytosis of oxidized LDL (oxLDL) by macrophages, rather than act as an independent receptor for oxLDL
As shown in fig. 1, oxLDL can stimulate the expression of SR-BI, LOX-1, TLR-4, CD64, CD32B and Siglec-1 on bone marrow-derived macrophages (BMMs) in a dose-dependent manner
Summary
Reduction of plasma level of oxidized LDL (oxLDL) may have a protective role in the initiation and progression of atherosclerosis (AS). Ishigaki et al [1] found that lowering oxLDL alone, rather than total LDL, affected atherogenesis in apolipoprotein Edeficient mice. Schiopu et al [3] found that recombinant antibodies to an oxLDL epitope can induce rapid and substantial regression of atherosclerosis in mice, possibly by stimulating lipid efflux and inhibiting macrophage recruitment. Binder et al [4] found that pneumococcal vaccination can decrease atherosclerotic lesion formation via molecular mimicry between streptococcus pneumoniae and oxLDL. These results together suggest that oxLDL has a major atherogenic role, and oxLDL removal might prevent the development of atherosclerosis, at least partly, due to inhibition of oxLDL incorporation into macrophages. As an adhesion molecular of Itype lectins, Siglec-1 is highly expressed on circulating monocytes and plaque macrophages of atherosclerotic patients, but the exact role of Siglec-1 has not been elucidated
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