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Immune complexes containing malondialdehyde (MDA) LDL induce apoptosis in human macrophages
- Source :
- Clinical immunology (Orlando, Fla.). 187
- Publication Year :
- 2017
-
Abstract
- Immune complexes (IC) containing predominantly malondialdehyde-LDL and the corresponding autoantibodies (MDA-LDL IC) predict acute cardiovascular events, while IC rich in oxidized LDL (oxLDL IC) predict cardiovascular disease progression. Our objective was to determine mechanisms that could explain these prognostic differences. We compared the effects of the interaction of oxLDL, MDA-LDL and the corresponding IC with human macrophages focusing on apoptosis, metalloproteinases, and proinflammatory cytokines. MDA-LDL IC induced higher degrees of apoptosis, higher levels of caspase-3 expression, and increased expression and release of MMP-1 and TNF compared to MDA-LDL, oxLDL, and oxLDL IC. The pro-apoptotic effects of MDA-LDL IC were inhibited by blocking TNFR 1 or FcγRI. Blocking FcγRI abrogated the induction and expression of MMPs and proinflammatory cytokines by MDA-LDL IC. In conclusion, the interaction of MDA-LDL IC with FcγRI triggers macrophage apoptosis and increased expression and release of TNF and MMP-1, which can lead to the rupture of unstable plaques.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Immunology
Gene Expression
Apoptosis
Antigen-Antibody Complex
030204 cardiovascular system & hematology
Matrix metalloproteinase
Proinflammatory cytokine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Internal medicine
Malondialdehyde
medicine
Immunology and Allergy
Humans
Chemokine CCL2
Autoantibodies
Tissue Inhibitor of Metalloproteinase-1
Caspase 3
Interleukin-6
Tumor Necrosis Factor-alpha
Macrophages
Receptors, IgG
Autoantibody
Arteriosclerosis
medicine.disease
Atherosclerosis
Plaque, Atherosclerotic
Lipoproteins, LDL
030104 developmental biology
Endocrinology
chemistry
Matrix Metalloproteinase 9
Cardiovascular Diseases
Receptors, Tumor Necrosis Factor, Type I
Cancer research
Disease Progression
Cytokines
lipids (amino acids, peptides, and proteins)
Tumor necrosis factor alpha
Matrix Metalloproteinase 1
Subjects
Details
- ISSN :
- 15217035
- Volume :
- 187
- Database :
- OpenAIRE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Accession number :
- edsair.doi.dedup.....790ef79906459a41f3c5bff6170514ce