title: Human platelets pathogen reduced with riboflavin and ultraviolet light do not cause acute lung injury in a two-event SCID mouse model.
abstract: BACKGROUND
  Pathogen reduction technologies (PRTs) can induce platelet (PLT) lesions that reduce PLT survival and recovery from circulation and may be associated with acute lung injury (ALI).
  
  
  METHODS
  Human PLTs (hPLTs) in plasma with or without single or multiple Mirasol PRT treatments were assessed in vitro by aggregation and percentage of P-selectin expression. In vivo studies included PLT recovery in SCID mice and assessment of ALI in a two-event mouse model in which the sensitizing event was lipopolysaccharide injection and the second event was infusion of Mirasol-treated hPLTs.
  
  
  RESULTS
  A single-dose Mirasol treatment (5 J/cm(2) ) did not induce any change in aggregation in response to adenosine 5'-diphosphate (ADP) while a five-times-repeat Mirasol treatment (5×) increased aggregation response to low concentration of ADP. Mirasol PLTs (1×-5×) had increased percentage of P-selectin-positive PLTs after treatment and decreased aggregation with TRAP as the agonist. In vivo recovery in SCID mice was reduced extensively with Mirasol treatments (1× and 5×). In the two-event model of ALI, only the 5× Mirasol PLTs accumulated in the lung and this was not accompanied by changes in lung histology or increases in MIP-2 levels in bronchoalveolar lavage fluid.
  
  
  CONCLUSIONS
  Mirasol PRT treatment induced PLT activation and reduced in vivo recovery in a SCID mouse model of transfusion. In our two-event mouse model of ALI, the 5× Mirasol hPLTs accumulated in the lung, but did not cause signs of ALI. The 1× Mirasol treatment did not lead to PLT lung accumulation or ALI in this model.
authors: Laboratory of Cellular Hematology, Division of Hematology, OBRR, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland.
authors: Xuan
authors: X
authors: Chi
authors: Li
authors: L
authors: Zhi
authors: Jaroslav G
authors: JG
authors: Vostal
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000382:microbiology* / Q000528:radiation effects; D001793:Blood Preservation / Q000379:methods; D017848:Blood-Borne Pathogens / Q000187:drug effects* / Q000528:radiation effects*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D050296:Microbial Viability; D017713:Platelet Transfusion / Q000009:adverse effects*; D012256:Riboflavin / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D012256:Riboflavin