title: In vitro and in vivo evidence for the role of elastase shedding of CD163 in human atherothrombosis.
abstract: OBJECTIVE
  CD163 is a macrophage receptor for haemoglobin-haptoglobin (Hb-Hp) complexes, responsible for the clearance of haemoglobin. We hypothesized that production of soluble CD163 (sCD163) may be due to proleolytic shedding of membrane CD163 by neutrophil elastase, reported to be increased in culprit atherosclerotic plaques. We analysed the relationship between CD163 solubilization and elastase in vitro, in macrophage culture, ex vivo in human atherosclerotic plaque samples, and in vivo, in plasma of patients with coronary artery disease.
  
  
  RESULTS
  Neutrophil elastase was shown to enhance CD163 shedding and to decrease the uptake of Hb-Hp complexes by cultured macrophages. In addition, cultured carotid endarterectomy samples showing features of intraplaque haemorrhage released more sCD163 and elastase/α1-antitrypsin (α1-AT) complexes than non-haemorrhagic plaques (n= 44). Plasma levels of sCD163 and neutrophil elastase (complexed with α1-AT) were measured in patients with an acute coronary syndrome (ACS, n= 42), stable angina pectoris (SAP, n= 28), or normal coronary angiograms without subclinical atherosclerosis (n= 21). Acute coronary syndrome patients had higher sCD163 and elastase/α1-AT complexes plasma concentrations than subjects without coronary atherosclerosis. Circulating sCD163 and elastase/α1-AT complexes were positively correlated in patients with ACS (r = 0.56, P< 0.0002) and SAP (r = 0.62, P< 0.0005).
  
  
  CONCLUSIONS
  Our results suggest that neutrophil elastase promotes CD163 shedding, resulting in a decreased clearance of Hb by macrophages, which may favour plaque destabilization. This may be reflected by increased plasma levels of sCD163 and elastase/α1-AT complexes which are positively correlated in patients with coronary artery disease.
authors: INSERM U, Paris, France.
authors: Juan Antonio
authors: JA
authors: Moreno
authors: Almudena
authors: A
authors: Ortega-Gómez
authors: Sandrine
authors: S
authors: Delbosc
authors: Nathalie
authors: N
authors: Beaufort
authors: Emmanuel
authors: E
authors: Sorbets
authors: Liliane
authors: L
authors: Louedec
authors: Marina
authors: M
authors: Esposito-Farèse
authors: Florence
authors: F
authors: Tubach
authors: Antonino
authors: A
authors: Nicoletti
authors: Philippe Gabriel
authors: PG
authors: Steg
authors: Jean-Baptiste
authors: JB
authors: Michel
authors: Laurent
authors: L
authors: Feldman
authors: Olivier
authors: O
authors: Meilhac