title: Phosphorylation of vasodilator-stimulated phosphoprotein prevents platelet-neutrophil complex formation and dampens myocardial ischemia-reperfusion injury.
abstract: BACKGROUND
  Recent work has suggested that the formation of platelet-neutrophil complexes (PNCs) aggravates the severity of inflammatory tissue injury. Given the importance of vasodilator-stimulated phosphoprotein (VASP) for platelet function, we pursued the role of VASP on the formation of PNCs and its impact on the extent of myocardial ischemia-reperfusion (IR) injury.
  
  
  RESULTS
  In initial in vitro studies we found that neutrophils facilitated the movement of platelets across endothelial monolayers. Phosphorylation of VASP reduced the formation of PNCs and transendothelial movement of PNCs. During myocardial IR injury, VASP(-/-) animals demonstrated reduced intravascular formation of PNCs and reduced presence of PNCs within the ischemic myocardial tissue. This was associated with reduced IR injury. Studies using platelet transfer and bone marrow chimeric animals showed that hematopoietic VASP expression was crucial for the intravascular formation of PNCs the presence of PNCs within ischemic myocardial tissue and the extent of myocardial IR injury. Furthermore, phosphorylation of VASP on Ser153 or Ser235 reduced intravascular PNC formation and presence of PNCs within ischemic myocardial tissue. This finding was associated with reduced myocardial IR injury.
  
  
  CONCLUSIONS
  Previously unappreciated, the phosphorylation of VASP performs a key function for the formation of PNCs that is crucially important for the extent of myocardial IR injury.
authors: Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tübingen, Germany.
authors: David
authors: D
authors: Köhler
authors: Andreas
authors: A
authors: Straub
authors: Thomas
authors: T
authors: Weissmüller
authors: Marion
authors: M
authors: Faigle
authors: Sarah
authors: S
authors: Bender
authors: Rainer
authors: R
authors: Lehmann
authors: Hans-Peter
authors: HP
authors: Wendel
authors: Julia
authors: J
authors: Kurz
authors: Ulrich
authors: U
authors: Walter
authors: Kai
authors: K
authors: Zacharowski
authors: Peter
authors: P
authors: Rosenberger