title: Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of 'soluble CD163' in plasma.
abstract: CD163 is the macrophage receptor for uptake of hemoglobin-haptoglobin complexes. The human receptor can be shed from the macrophage surface owing to a cleavage site for the inflammation-inducible TACE/ADAM17 enzyme. Accordingly, plasma 'soluble CD163' (sCD163) has become a biomarker for macrophage activity and inflammation. The present study disclosed that 10% of sCD163 in healthy persons is actually extracellular vesicle (EV)-associated CD163 not being cleaved and shed. Endotoxin injection of human volunteers caused a selective increase in the ectodomain CD163, while septic patients exhibited high levels of both soluble ectodomain CD163 and extracellular vesicle (EV) CD163, the latter representing up 60% of total plasma CD163. A poor prognosis of septic patients measured as the sequential organ failure assessment (SOFA) score correlated with the increase in membrane-associated CD163. Our results show that soluble ectodomain CD163 and EV CD163 in plasma are part of separate macrophage response in the context of systemic inflammation. While that soluble ectodomain CD163 is released during the acute systemic inflammatory response, this is not the case for EV CD163 that instead may be released during a later phase of the inflammatory response. A separate measurement of the two forms of CD163 constituting 'soluble CD163' in plasma may therefore add to the diagnostic and prognostic value.
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Anders
authors.initials: A
authors.lastname: Etzerodt
authors.affiliation: Centre of Inflammation and Metabolism, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ronan M G
authors.initials: RM
authors.lastname: Berg
authors.affiliation: Department of Intensive Care, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ronni R
authors.initials: RR
authors.lastname: Plovsing
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Morten N
authors.initials: MN
authors.lastname: Andersen
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Bebien
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Habbeddine
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280, Marseille, France.
authors.forename: Toby
authors.initials: T
authors.lastname: Lawrence
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Department of Biomedicine, University of Aarhus, Aarhus, Denmark.|Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.|Department of Molecular Medicine, University of Southern Denmark, Denmark.
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000737:chemistry; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000737:chemistry; D015415:Biomarkers / Q000097:blood*; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity; D000067128:Extracellular Vesicles / Q000737:chemistry*; D005260:Female; D006242:Haptoglobins / Q000737:chemistry / Q000235:genetics; D064368:Healthy Volunteers; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000139:chemically induced; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics; D011956:Receptors, Cell Surface / Q000097:blood* / Q000737:chemistry; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D004731:Endotoxins; D006242:Haptoglobins; D006454:Hemoglobins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C035492:haptoglobin-hemoglobin complex