title: Annexin V homodimer protects against ischemia reperfusion-induced acute lung injury in lung transplantation.
abstract: OBJECTIVE
  We hypothesized that administration of a homodimer of recombinant annexin V, diannexin, could shield phosphatidylserine on the endothelium, and inhibit leukocyte and platelet adhesion, thereby potentially reducing ischemia reperfusion injury (IRI) in lung transplantation. This hypothesis was tested using a rat syngeneic single left-lung transplant model.
  
  
  METHODS
  Rats were randomly assigned to receive diannexin (DN group; n = 10) or normal saline (control group; n = 10). Diannexin (1000 μg/kg) was administered to the donor lung in the pulmonary flush solution, and to the recipient intravenously, 5 minutes after initiation of reperfusion. Grafts were reperfused for 2 hours.
  
  
  RESULTS
  The transplanted grafts in the DN group performed significantly better in gas exchange with higher partial pressure of oxygen (control group: 179 ± 121 vs DN group: 330 ± 54 mm Hg; P = .007) and lower partial pressure of carbon dioxide (control: 55.1 ± 26 vs DN: 34.2 ± 11 mm Hg; P = .04), as well as lower peak airway pressure (control: 20.5 ± 8.5 vs DN: 12.0 ± 7.9 cm H2O; P = .035) after 2 hours of reperfusion. Wet-to-dry lung weight ratio (P = .054), and alveolar fibrin deposition score (P = .04), were reduced in the DN group. Caspase-cleaved cytokeratin 18 in plasma (a marker of epithelial apoptosis) was significantly reduced in the DN group (P = .013). Furthermore, gene-expression levels of proinflammatory cytokines in the transplanted graft, including interleukin-6 (P = .04) and macrophage inflammatory protein 2 (P = .03) were significantly decreased in the DN group.
  
  
  CONCLUSIONS
  A homodimer of recombinant annexin V reduced ischemia reperfusion injury in a lung transplant animal model, by reducing cell death and tissue inflammation.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hyunhee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Oishi
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Manyin
authors.initials: M
authors.lastname: Chen
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ilker
authors.initials: I
authors.lastname: Iskender
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jin
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohsumi
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zehong
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: Shaf.Keshavjee@uhn.ca.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053538:Keratin-18 / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D017304:Annexin A5; D016207:Cytokines; D018836:Inflammation Mediators; D053538:Keratin-18; D010446:Peptide Fragments; D020011:Protective Agents; C519264:diannexin, human; D005337:Fibrin
keywords: apoptosis; diannexin; ischemia reperfusion injury; primary graft dysfunction