title: Elevated soluble CD163 in gestational diabetes mellitus: secretion from human placenta and adipose tissue.
abstract: Recently soluble CD163 (sCD163), a cleaved form of the macrophage receptor CD163, was identified as a macrophage-specific risk-predictor for developing Type 2 Diabetes. Here, we investigate circulating levels of sCD163 in gestational diabetes mellitus (GDM). Furthermore, given the role of the placenta in the pathogenesis of GDM, we assessed placental contribution to sCD163 secretion. Paired maternal (venous) and umbilical vein blood samples from GDM (n = 18) and Body Mass Index (BMI) matched control women (n = 20) delivered by caesarean section at 39-40 week gestation were assessed for circulating levels of sCD163, Tumour necrosis factor alpha (TNF-α) and Interleukin 6 (IL-6). Media from explant culture of maternal subcutaneous fat and corresponding placental tissues were assayed for these same molecules. CD163 positive cell numbers were determined in placental and adipose tissues of GDM and control women. We found significantly elevated circulating sCD163 levels in GDM mothers (688.4±46.9 ng/ml vs. 505.6±38.6 ng/ml) and their offspring (418.2±26.6 ng/ml vs. 336.3±24.4 ng/ml [p<0.05 for both]) as compared to controls, together with elevated circulating TNF-α and IL-6 levels. Moreover, both GDM placentae (268.1±10.8 ng/ml/mg vs. 187.6±20.6 ng/ml/mg) and adipose explants (41.1±2.7 ng/ml/mg vs. 26.6±2.4 ng/ml/mg) released significantly more sCD163 than controls. Lastly, significantly more CD163 positive cells were observed in GDM placentae (25.7±1.1 vs. 22.1±1.2) and adipose tissue (19.1±1.1 vs 12.7±0.9) compared to controls. We describe elevated sCD163 levels in GDM and identify human placenta as a novel source of sCD163 suggesting that placental tissues might contribute to the increased levels of circulating sCD163 in GDM pregnancies.
authors.affiliation: Department of Pathology, Dow International Medical College, Karachi, Pakistan; Divisions of Reproduction and Metabolic & Vascular Health, Warwick Medical School, Coventry, West Midlands, United Kingdom.
authors.forename: Muhammad Furqan
authors.initials: MF
authors.lastname: Bari
authors.affiliation: Divisions of Reproduction and Metabolic & Vascular Health, Warwick Medical School, Coventry, West Midlands, United Kingdom; Departments of Pathology & Endocrinology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Weickert
authors.affiliation: Divisions of Reproduction and Metabolic & Vascular Health, Warwick Medical School, Coventry, West Midlands, United Kingdom.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sivakumar
authors.affiliation: Departments of Pathology & Endocrinology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom.
authors.forename: Sean G
authors.initials: SG
authors.lastname: James
authors.affiliation: Departments of Pathology & Endocrinology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom.
authors.forename: David R J
authors.initials: DR
authors.lastname: Snead
authors.affiliation: Divisions of Reproduction and Metabolic & Vascular Health, Warwick Medical School, Coventry, West Midlands, United Kingdom.
authors.forename: Bee Kang
authors.initials: BK
authors.lastname: Tan
authors.affiliation: Divisions of Reproduction and Metabolic & Vascular Health, Warwick Medical School, Coventry, West Midlands, United Kingdom; Departments of Pathology & Endocrinology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, West Midlands, United Kingdom.
authors.forename: Harpal Singh
authors.initials: HS
authors.lastname: Randeva
authors.affiliation: Divisions of Reproduction and Metabolic & Vascular Health, Warwick Medical School, Coventry, West Midlands, United Kingdom; Department of Medicine & Endocrinology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Claire Cecile
authors.initials: CC
authors.lastname: Bastie
authors.affiliation: Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford, Oxfordshire, United Kingdom.
authors.forename: Manu
authors.initials: M
authors.lastname: Vatish
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D010920:Placenta / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha