title: Inhibition of Plexin C1 Protects Against Hepatic Ischemia-Reperfusion Injury.
abstract: Hepatic ischemia-reperfusion injury is a disease pattern that is associated with an acute inflammatory reaction. It is well known that neutrophils play an essential role in the early phase of hepatic ischemia-reperfusion injury and determine the extent of tissue damage. Hepatic ischemia-reperfusion injury can result in organ failure, which is linked to high mortality. Recent data indicate that the neuronal guidance receptor Plexin C1 is involved in the control of the acute inflammatory response and, as such, modulates the transmigration of neutrophils. Hence, we investigated the functional role of Plexin C1 in a mouse model of early hepatic ischemia-reperfusion injury.
  
  
  
  Animal study.
  
  
  
  University experimental laboratory.
  
  
  
  Wild-type, PLXNC1 and chimeric mice.
  
  
  
  Hepatic ischemia-reperfusion injury or sham operation.
  
  
  
  We found that the functional inhibition of Plexin C1 in wild-type mice treated with an anti-Plexin C1 antibody and a Semaphorin 7A peptide reduced hepatic ischemia-reperfusion injury, as measured by the levels of lactate dehydrogenase, aspartate, and alanine aminotransferase. This reduction in ischemia-reperfusion injury was accompanied by reduced numbers of neutrophils in ischemic hepatic tissue and reduced serum levels of inflammatory cytokines. Experiments using Plexin C1 receptor-deficient (PLXNC1) mice also demonstrated decreased hepatic ischemia-reperfusion injury. Studies of chimeric mice revealed that the hematopoietic Plexin C1 knockout is crucial for reducing the extent of hepatic ischemia-reperfusion injury.
  
  
  
  These results describe a role for Plexin C1 during ischemia-reperfusion injury, highlight the role of hematopoietic Plexin C1 in the development of hepatic ischemia-reperfusion injury, and suggest that Plexin C1 is a potential drug target.
authors.affiliation: 1Department of Anaesthesiology and Intensive Care Medicine, Tübingen University Hospital, Eberhard-Karls University Tübingen, Tübingen, Germany. 2Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt am Main, Johann Wolfgang Goethe University, Tübingen, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: König
authors.forename: Tiago
authors.initials: T
authors.lastname: Granja
authors.forename: Veit-Simon
authors.initials: VS
authors.lastname: Eckle
authors.forename: Valbona
authors.initials: V
authors.lastname: Mirakaj
authors.forename: David
authors.initials: D
authors.lastname: Köhler
authors.forename: Martin
authors.initials: M
authors.lastname: Schlegel
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenberger
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology; D001224:Aspartic Acid / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000819:agonists*; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D039961:Semaphorins / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D018836:Inflammation Mediators; C118753:SEMA7A protein, human; D039961:Semaphorins; D001224:Aspartic Acid; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase