title: Prestorage leukoreduction prevents accumulation of matrix metalloproteinase 9 in stored blood.
abstract: OBJECTIVE
  Transfusion of aged stored blood is associated with many neutrophil proinflammatory effects. The mechanism of these effects remains to be elucidated. The purpose of this study was to determine whether matrix metalloproteinases accumulate in packed red blood cells during storage and are responsible for some of the neutrophil proinflammatory events, and to determine whether prestorage leukoreduction prevents accumulation of matrix metalloproteinases and attenuates proinflammatory effects of stored packed red blood cells.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  Healthy human volunteers.
  
  
  METHODS
  Units of blood were drawn from healthy volunteers. Half of each unit was filtered for leukoreduction, removing 99.9% of leukocytes. At biweekly intervals, aliquots were removed from packed red blood cell units, and the plasma fraction was isolated for assays. Plasma was assayed for specific molecules or incubated with isolated neutrophils, with or without a matrix metalloproteinase 9 inhibitor.
  
  
  METHODS
  Concentrations of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinase 1; matrix metalloproteinase 9 activity; and neutrophil apoptosis.
  
  
  RESULTS
  Concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 but not matrix metalloproteinase 2 increased over time. This accumulation was abolished by leukoreduction. Matrix metalloproteinase 9 accumulated in an active form. Both leukoreduction and matrix metalloproteinase 9 inhibition reversed stored packed red blood cell-induced, delayed neutrophil apoptosis.
  
  
  CONCLUSIONS
  Storage of packed red blood cells for 14 days or more is associated with increases in the concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1, with the enzyme in excess of its inhibitor. Prestorage leukoreduction prevents this accumulation. Delayed neutrophil apoptosis related to packed red blood cell plasma appears to be due, in part, to matrix metalloproteinase 9. Leukoreduction can help prevent the effects of matrix metalloproteinase 9 on neutrophil apoptosis.
authors.affiliation: George Washington University School of Medicine, Washington, DC, USA.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Frake
authors.forename: Hadley E
authors.initials: HE
authors.lastname: Smith
authors.forename: Lii-Fang
authors.initials: LF
authors.lastname: Chen
authors.forename: Walter L
authors.initials: WL
authors.lastname: Biffl
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis; D001771:Blood Banks; D001793:Blood Preservation / Q000379:methods*; D006801:Humans; D007937:Leukapheresis / Q000379:methods*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D013048:Specimen Handling / Q000379:methods
chemical_list: D020780:Matrix Metalloproteinase 9