ABSTRACT
Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14+ HLA-DRneg/low) has been hampered by the lack of positive cell-surface markers. In order to identify positive markers for Mo-MDSC, we performed microarray analysis comparing Mo-MDSC cells from healthy subjects versus CD14+ HLA-DRhigh monocytes. We have identified the surface ectoenzyme Vanin-2(VNN2) protein as a novel biomarker highly-enriched in healthy subjects Mo-MDSC. Indeed, healthy subjects Mo-MDSC cells expressed 68 % VNN2, whereas only 9% VNN2 expression was observed on CD14+ HLA-DRhigh cells (n = 4 p < 0.01). The top 10 percent positive VNN2 monocytes expressed CD33 and CD11b while being negative for HLA-DR, CD3, CD15, CD19 and CD56, consistent with a Mo-MDSC phenotype. CD14+VNN2high monocytes were able to inhibit CD8 T cell proliferation comparably to traditional Mo-MDSC at 51 % and 48 % respectively. However, VNN2 expression on CD14+ monocytes from glioma patients was inversely correlated to their grade. CD14+VNN2high monocytes thus appear to mark a monocytic population similar to Mo-MDSC only in healthy subjects, which may be useful for tumor diagnoses.
Subject(s)
Amidohydrolases/metabolism , Cell Adhesion Molecules/metabolism , Glioma/diagnosis , Lipopolysaccharide Receptors/metabolism , Monocytes/immunology , Myeloid-Derived Suppressor Cells/immunology , Biomarkers/analysis , CD8-Positive T-Lymphocytes/immunology , Cell Proliferation/physiology , GPI-Linked Proteins/metabolism , Glioma/pathology , HLA-DR Antigens/metabolism , Humans , Lymphocyte Activation/immunology , Membrane Proteins/metabolism , Neoplasm Grading , Protein Array Analysis , Sialic Acid Binding Ig-like Lectin 3/metabolismSubject(s)
Hospices/standards , Quality Improvement , Consumer Behavior/statistics & numerical data , Family , Hospices/organization & administration , Hospices/statistics & numerical data , Humans , Quality Assurance, Health Care/methods , Quality Assurance, Health Care/organization & administration , Quality Improvement/organization & administration , Quality Improvement/statistics & numerical dataABSTRACT
BACKGROUND: Recent studies report independent associations between psoriasis, cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from activated myeloid cells is associated with CV risk mainly through lipid oxidation, induction of endothelial dysfunction and release of IL-12 from macrophages. OBJECTIVES: To elucidate associations between psoriasis and conventional CV risk factors. METHODS: We performed a cross-sectional study of 100 psoriasis patients and 53 controls, group matched on age, gender and body mass index, to assess levels of MPO in serum, as well as immunohistochemical staining from psoriasis skin lesions, psoriasis uninvolved skin, and normal skin. RESULTS: Although the groups did not differ on waist circumference, glucose, cholesterol, triglycerides, creatinine or personal history of CV events, psoriasis patients had significantly higher waist-to-hip ratios, blood pressures, proportion of current smokers, and lower high density lipoprotein level than controls. Serum MPO level was elevated 2.5 fold (P<0.001) in psoriasis patients, even after adjusting for the CV risk factors on which the groups differed. MPO did correlate with coronary artery calcification, carotid plaque, carotid intima media thickness and flow mediated dilation, but did not correlate with psoriasis severity. However, MPO was highly expressed in lesional psoriatic skin and colocalized predominantly with CD45(+) CD11b(+) leukocytes. CD11b(+) cell density correlated with circulation MPO levels. CONCLUSION: Lesional skin CD11b(+) leukocytes activated to generate MPO may contribute to serum levels of MPO. Lesional CD11b(+) cell activity may be an alternative measure of disease burden to PASI that underlies the MPO biomarker for systemic inflammation related to Cardiovascular Disease.
