title: The instant blood-mediated inflammatory reaction characterized in hepatocyte transplantation.
abstract: BACKGROUND
  Hepatocyte transplantation (HcTx) has proven to be a safe procedure, although the functional results have been unsatisfactory, probably due to insufficient engraftment or a loss of transplanted mass or function. In this study, we investigate whether hepatocytes in contact with blood induce an inflammatory reaction leading to, similar to what happens in clinical islet transplantation, an instant blood-mediated inflammatory reaction (IBMIR) resulting in an early loss of transplanted cells.
  
  
  METHODS
  By using an experimental model that mimics the portal vein blood flow, we could study different parameters reflecting the effects on the innate immunity elicited by hepatocytes in contact with ABO-matched human blood.
  
  
  RESULTS
  We report that all aspects of the IBMIR such as platelet and granulocyte consumption, coagulation, and complement activation were demonstrated. Addition of various specific inhibitors of coagulation allowed us to clearly delineate the various stages of the hepatocyte-triggered IBMIR and show that the reaction was triggered by tissue factor. Analysis of a case of clinical HcTx showed that hepatocyte-induced IBMIR also occurs in vivo. Both the inflammatory and the coagulation aspects were controlled by low-molecular-weight dextran sulfate.
  
  
  CONCLUSIONS
  Isolated hepatocytes in contact with blood induce the IBMIR in vitro, and there are indications that these events are also relevant in vivo. According to these findings, HcTx would benefit from controlling a wider range of signals from the innate immune system.
authors.affiliation: Department of Women's and Children's Health, Peadiatric Surgery, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Elisabet K
authors.initials: EK
authors.lastname: Gustafson
authors.forename: Graciela
authors.initials: G
authors.lastname: Elgue
authors.forename: Robin D
authors.initials: RD
authors.lastname: Hughes
authors.forename: Ragai R
authors.initials: RR
authors.lastname: Mitry
authors.forename: Javier
authors.initials: J
authors.lastname: Sanchez
authors.forename: Ulf
authors.initials: U
authors.lastname: Haglund
authors.forename: Staffan
authors.initials: S
authors.lastname: Meurling
authors.forename: Anil
authors.initials: A
authors.lastname: Dhawan
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D000017:ABO Blood-Group System; D001777:Blood Coagulation; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000494:pharmacology; D022781:Hepatocytes / Q000276:immunology* / Q000637:transplantation*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology* / Q000517:prevention & control; D011183:Postoperative Complications / Q000209:etiology*; D013925:Thromboplastin / Q000502:physiology
chemical_list: D000017:ABO Blood-Group System; D013925:Thromboplastin; D016264:Dextran Sulfate