title: Ultraviolet B light-exposed human platelets mediate acute lung injury in a two-event mouse model of transfusion.
abstract: BACKGROUND
  Ultraviolet B (UVB) light has been used alone on platelet (PLT) transfusion products to prevent alloimmunization or with chemical sensitizers to reduce pathogens. Such processing can damage PLTs and potentiate their storage lesion. Transfusion-related acute lung injury (ALI) has occurred in patients whose underlying condition led to an inflamed endothelium and who were transfused with products that contained either HLA or HNA antibodies or biologic modifiers such as lipids or antigens from stored cells. Clinical trials of UV-treated PLTs in patients with thrombocytopenia generated controversy regarding association of these cells with respiratory distress. We evaluated whether UVB PLTs could mediate ALI in an animal model of ALI.
  
  
  METHODS
  We used a two-event animal model where the sensitizing event was lipopolysaccharide (LPS) and the second event was infusion of human PLTs or UVB human PLTs (2.4 J/cm(2) ). Infused human PLTs were followed with whole animal imaging, lung histology, confocal microscopy, lung water, and changes in bronchoalveolar lavage fluid (BALF) related to ALI.
  
  
  RESULTS
  In LPS-treated mice UVB human PLTs accumulated in the lungs and were associated with ALI manifested by increased protein and white blood cells (WBCs) in BALF. Untreated human PLTs did not accumulate in the lungs or increase BALF protein or WBC counts.
  
  
  CONCLUSIONS
  We provide a proof of principle that UVB human PLTs can accumulate in lungs of LPS-primed animals and mediate ALI. PLTs exposed to high doses of UVB could potentially mediate similar effects in patients predisposed with sepsis or other causes of endothelial cell inflammation.
authors.affiliation: Laboratory of Cellular Hematology, Division of Hematology, OBRR, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20892, USA.
authors.forename: Monique P
authors.initials: MP
authors.lastname: Gelderman
authors.forename: Xuan
authors.initials: X
authors.lastname: Chi
authors.forename: Li
authors.initials: L
authors.lastname: Zhi
authors.forename: Jaroslav G
authors.initials: JG
authors.lastname: Vostal
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology*; D000818:Animals; D001792:Blood Platelets / Q000528:radiation effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D023421:Models, Animal; D017713:Platelet Transfusion / Q000009:adverse effects*; D014466:Ultraviolet Rays
chemical_list: D008070:Lipopolysaccharides