Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of 'soluble CD163' in plasma
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Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of 'soluble CD163' in plasma. / Etzerodt, Anders; Berg, Ronan M G; Plovsing, Ronni R; Andersen, Morten N; Bebien, Magali; Habbeddine, Mohamed; Lawrence, Toby; Møller, Holger J.; Moestrup, Søren K.
I: Scientific Reports, Bind 7, 40286, 2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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T1 - Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of 'soluble CD163' in plasma
AU - Etzerodt, Anders
AU - Berg, Ronan M G
AU - Plovsing, Ronni R
AU - Andersen, Morten N
AU - Bebien, Magali
AU - Habbeddine, Mohamed
AU - Lawrence, Toby
AU - Møller, Holger J.
AU - Moestrup, Søren K.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Antigens, CD/blood
KW - Antigens, Differentiation, Myelomonocytic/blood
KW - Biomarkers/blood
KW - Endotoxins/administration & dosage
KW - Extracellular Vesicles/chemistry
KW - Female
KW - Haptoglobins/chemistry
KW - Healthy Volunteers
KW - Hemoglobins/chemistry
KW - Humans
KW - Inflammation/blood
KW - Macrophages/drug effects
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Protein Isoforms/genetics
KW - Receptors, Cell Surface/blood
U2 - 10.1038/srep40286
DO - 10.1038/srep40286
M3 - Journal article
C2 - 28084321
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 40286
ER -
ID: 236992345