title: Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury.
abstract: OBJECTIVE
  The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors.
  
  
  METHODS
  Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak.
  
  
  RESULTS
  There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak.
  
  
  CONCLUSIONS
  Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.
authors.affiliation: Departments of Pulmonary Sciences and Critical Care Medicine, University of Colorado at Denver, USA ; Department of Medicine, University of Colorado at Denver, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Maloney
authors.affiliation: Department of Pediatrics, University of Colorado at Denver, USA ; Department of Pathology, University of Colorado at Denver, USA ; University of Colorado School of Medicine; the Center for Cancer and Blood Disorders, Children's Hospital Colorado, USA ; Bonfils Blood Center, University of Colorado at Denver, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Ambruso
authors.affiliation: Department of Internal Medicine, Commonwealth University of Virginia, USA.
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Voelkel
authors.affiliation: Department of Medicine, University of Colorado at Denver, USA ; Department of Pediatrics, University of Colorado at Denver, USA ; Department of Surgery, University of Colorado at Denver, USA ; University of Colorado School of Medicine; the Center for Cancer and Blood Disorders, Children's Hospital Colorado, USA ; Bonfils Blood Center, University of Colorado at Denver, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
keywords: Apheresis; Leukocytes; Lung injury; Platelets; Storage; Transfusion; Vascular endothelial growth factor