title: Increased MerTK expression in circulating innate immune cells of patients with septic shock.
abstract: OBJECTIVE
  A new pathway of three protein tyrosine kinase receptors, namely, the TAM receptor family [Tyro-3, Axl and Mer tyrosine kinase (MerTK)], has recently been described to negatively control immune responses. The objective of this prospective, observational, clinical study was to investigate the expression patterns of TAM receptors in circulating white blood cells collected from patients with septic shock.
  
  
  METHODS
  The expression of TAM receptors was measured by flow cytometry in circulating leukocytes from patients with septic shock sampled on days (D) 1-2 (n = 47) and D3-4 (n = 37) after the onset of shock, severe trauma patients at D1-2 after trauma (n = 51) and healthy individuals (n = 23).
  
  
  RESULTS
  On D1-2 after injury, MerTK was overexpressed in monocytes and neutrophils collected from patients with septic shock in comparison with those collected from healthy volunteers and trauma patients. This phenomenon was also observed for mRNA. Conversely, the expression of Tyro-3 and Axl was higher in monocytes from trauma patients versus healthy volunteers or those in septic shock. MerTK expression between D1-2 and D3-4 remained elevated in patients suffering from septic shock who died or developed an intensive care unit-acquired infection, whereas it decreased in patients who recovered uneventfully. This in vivo observed expression pattern was reproduced ex vivo after the incubation of healthy volunteer cells with plasma from septic shock or trauma patients.
  
  
  CONCLUSIONS
  MerTK expression in circulating innate immune cells is increased in patients with septic shock in comparison with healthy volunteers and trauma patients. Persistent MerTK overexpression after septic shock is associated with adverse outcome. The role of this family of receptors in the pathophysiology of injury-induced immune dysfunctions deserves to be specifically investigated.
authors.affiliation: Laboratoire d'Immunologie, Hôpital E. Herriot, Hospices Civils de Lyon, 5 place d'Arsonval, 69437, Lyon cedex 03, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Guignant
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.forename: Séverine
authors.initials: S
authors.lastname: Planel
authors.forename: Julie
authors.initials: J
authors.lastname: Demaret
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gouel-Chéron
authors.forename: Christophe
authors.initials: C
authors.lastname: Nougier
authors.forename: Arnaud
authors.initials: A
authors.lastname: Friggeri
authors.forename: Bernard
authors.initials: B
authors.lastname: Allaouchiche
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D012772:Shock, Septic / Q000097:blood* / Q000276:immunology*; D014947:Wounds and Injuries / Q000097:blood* / Q000276:immunology*; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human