title: Imaging the dynamic platelet-neutrophil response in sterile liver injury and repair in mice.
abstract: Although platelets have been extensively studied in hemostasis and inflammation, their role is not well understood in sterile liver injury and repair. Using a thermally induced focal liver injury and repair model and multichannel spinning disk confocal microscopy allowed visualization of the dynamic behavior of platelets and neutrophils in this insult. Platelets instantaneously adhered to molecularly altered sinusoidal endothelium adjacent to the afflicted area, paving approximately 200 µm abutting the injury. Platelets remained adherent for at least 4 hours, but dissipated by 8 hours. The early recruitment occurred by GPIIbIIIa (CD41) and the later recruitment was dependent upon both GPIIbIIIa and GPIb (CD42B). Platelets did not occlude the vessels, but rather paved the altered endothelium. Endothelin-induced vasoconstriction by hepatic stellate cells, and not platelet accumulation or coagulation, was responsible for temporarily restricted perfusion around the injury. Neutrophils crawled into the injury from significant distances through the sinusoids. The crawling neutrophils required the platelet-paved endothelium given that very little neutrophil recruitment was noted in thrombocytopenic or CD41-deficient mice. As platelets slowly dissipated, neutrophil recruitment was also halted. Previous work suggested that platelets binding to immobilized neutrophils induced neutrophil extracellular trap (NET) formation in response to infection as well as during thrombosis and other forms of sterile injury. In this model of neutrophils crawling on immobilized platelets, very few NETs were observed and no additional injury was noted. In fact, GPIIbIIIa-deficient mice had delayed repair.
  
  
  CONCLUSIONS
  In a liver model of sterile injury and repair, platelets play a critical role in forming a substratum and pave the way for neutrophils to enter the injured site for subsequent repair.
authors.affiliation: Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada.|Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Slaba
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.|Department of Evolutionary Immunology, Jagiellonian University, Krakow, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kolaczkowska
authors.affiliation: Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada.|Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.|Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Braedon
authors.initials: B
authors.lastname: McDonald
authors.affiliation: Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.|Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Woo-Yong
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada.|Calvin, Phoebe & Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.|Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000502:physiology; D008099:Liver / Q000293:injuries*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D040201:Platelet Membrane Glycoprotein IIb / Q000502:physiology
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D040201:Platelet Membrane Glycoprotein IIb