title: Platelet aggregation but not activation and degranulation during the acute post-ischemic reperfusion phase in livers with no underlying disease.
abstract: BACKGROUND
  Platelets and P-selectin (CD62P) play an unequivocal role in the pathology of hepatic ischemia/reperfusion (I/R) injury. Inhibition or knock-out of P-selectin or immunodepletion of platelets results in amelioration of post-ischemic inflammation, reduced hepatocellular damage, and improved survival. However, P-selectin expression on platelets and endothelial cells, which concurs with platelet activation, has never been clearly demonstrated in I/R-subjected livers.
  
  
  OBJECTIVE
  To determine whether platelets become activated and degranulate in the acute phase of liver I/R and whether the platelets interact with neutrophils.
  
  
  METHODS
  Hepatic I/R was induced in male C57BL/6J mice (N = 12) using 37.5-min ischemia time. Platelets, endothelial cells, and neutrophils were fluorescently labeled by systemic administration of non-blocking antibodies. Cell kinetics were monitored by intravital spinning disk confocal microscopy during 90 min of reperfusion. Image analysis and quantification was performed with dedicated software.
  
  
  RESULTS
  Platelets adhered to sinusoids more extensively in post-ischemic livers compared to livers not subjected to I/R and formed aggregates, which occurred directly after ischemia. Platelets and endothelial cells did not express P-selectin in post-ischemic livers. There was no interaction between platelets and neutrophils.
  
  
  CONCLUSIONS
  Platelets aggregate but do not become activated and do not degranulate in post-ischemic livers. There is no platelet-neutrophil interplay during the early reperfusion phase in a moderate model of hepatic I/R injury. The mechanisms underlying the biological effects of platelets and P-selectin in this setting warrant further investigation.
  I/R in surgical liver patients may compromise outcome due to post-ischemic oxidative stress and sterile inflammation. Both processes are mediated in part by platelets. Understanding platelet function during I/R is key to developing effective interventions for I/R injury and improving clinical outcomes.
authors.affiliation: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rowan F
authors.initials: RF
authors.lastname: van Golen
authors.affiliation: Live Cell Imaging Facility, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Stevens
authors.affiliation: Live Cell Imaging Facility, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Pina
authors.initials: P
authors.lastname: Colarusso
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Jaeschke
authors.affiliation: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michal
authors.initials: M
authors.lastname: Heger
keywords: CD62P or P-selectin; hepatic ischemia/reperfusion injury; platelet-neutrophil interactions; sterile inflammation