ABSTRACT
BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular morbidity and mortality. SLE patients have increased prevalence of subclinical atherosclerosis, although the mechanisms of this observation remain unclear. Considering the emerging role of monocytes in atherosclerosis, we aimed to investigate the relationship between subclinical atherosclerosis, endothelial dysfunction and the phenotype of peripheral blood monocytes in SLE patients. METHODS: We characterized the phenotype of monocyte subsets defined by the expression of CD14 and CD16 in 42 patients with SLE and 42 non-SLE controls. Using ultrasonography, intima-media thickness (IMT) of carotid arteries and brachial artery flow-mediated dilation (FMD) as well as nitroglycerin-induced dilation (NMD) were assessed. RESULTS: Patients with SLE had significantly, but only modestly, increased IMT when compared with non-SLE controls (median (25th/75th percentile) 0.65 (0.60/0.71) mm vs 0.60 (0.56/0.68) mm; p < 0.05). Importantly, in spite of early atherosclerotic complications in the studied SLE group, marked endothelial dysfunction was observed. CD14dimCD16+proinflammatory cell subpopulation was positively correlated with IMT in SLE patients. This phenomenon was not observed in control individuals. Interestingly, endothelial dysfunction assessed by FMD was not correlated with any of the studied monocyte subsets. CONCLUSIONS: Our observations suggest that CD14dimCD16+monocytes are associated with subclinical atherosclerosis in SLE, although the mechanism appears to be independent of endothelial dysfunction.
Subject(s)
Atherosclerosis/etiology , Brachial Artery/physiopathology , Carotid Artery Diseases/etiology , Endothelium, Vascular/physiopathology , Lipopolysaccharide Receptors/blood , Lupus Erythematosus, Systemic/complications , Monocytes/metabolism , Receptors, IgG/blood , Vasodilation , Adult , Aged , Asymptomatic Diseases , Atherosclerosis/blood , Atherosclerosis/diagnostic imaging , Atherosclerosis/physiopathology , Biomarkers/blood , Brachial Artery/diagnostic imaging , Carotid Arteries/diagnostic imaging , Carotid Artery Diseases/blood , Carotid Artery Diseases/diagnostic imaging , Carotid Intima-Media Thickness , Case-Control Studies , Female , Flow Cytometry , GPI-Linked Proteins/blood , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Male , Middle Aged , Phenotype , Predictive Value of Tests , Risk Factors , Young AdultABSTRACT
Efficient removal of apoptotic polymorphonuclear leukocytes (PMNs) is an important step in the resolution of inflammation, which protects tissues from the noxious contents of dying cells. While the impairment of apoptotic PMNs removal has been demonstrated for macrophages in systemic lupus erythematosus (SLE), recent studies show that monocytes are also capable of such phagocytosis, although their involvement in SLE is not clear. Therefore, we characterized phagocytosis of apoptotic PMNs by monocytes in 22 patients with SLE and 22 healthy controls. Using flow cytometry we demonstrate that in SLE peripheral blood monocytes show impaired phagocytosis of autologous apoptotic PMNs, while they efficiently engulf apoptotic PMNs isolated from healthy subjects. Monocytes CD14highCD16+ and CD14dimCD16+ more efficiently interacted with apoptotic neutrophils than CD16- cells both in SLE and healthy subjects. Monocytes in SLE showed modestly decreased expression of CD35 and CD91 and increased expression of T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3); however, these differences were evident mainly in selected subsets of monocytes (CD16+) while defects in phagocytosis were observed in all monocyte subsets. Apoptotic cell-dependent induction of lipopolysaccharide (LPS) stimulated production of anti-inflammatory cytokine IL-10 by peripheral blood mononuclear cells (PBMC) was blunted in SLE while the production of pro-inflammatory cytokine TNF-α was unchanged.
Subject(s)
Antigens, CD/analysis , Lupus Erythematosus, Systemic/immunology , Monocytes/chemistry , Monocytes/immunology , Phagocytosis , Adult , Apoptosis , Case-Control Studies , Female , Hepatitis A Virus Cellular Receptor 2 , Humans , Interleukin-10/biosynthesis , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Lipopolysaccharide Receptors/analysis , Lipopolysaccharides/pharmacology , Low Density Lipoprotein Receptor-Related Protein-1/analysis , Male , Membrane Proteins/analysis , Middle Aged , Neutrophils/physiology , Receptors, Complement 3b/analysis , Receptors, IgG/analysis , Tumor Necrosis Factor-alpha/biosynthesis , Young AdultABSTRACT
Twenty-two children with bronchial asthma and positive skin tests to house-dust allergen were subjected to a bronchial provocation test with the allergen, and both bronchial reactions and serum complement hemolytic activity were measured at different intervals after the challenge. Changes in complement hemolytic activity did not correspond either with early or late bronchial reaction to the allergen. A reproducible drop in complement hemolytic activity after allergen challenge was observed in eight patients and could be prevented in four out of seven patients by sodium cromoglycate. The duration of early bronchial obstructive reaction was longer in tests where parallel complement changes were observed.
