Prestorage leukoreduction prevents accumulation of matrix metalloproteinase 9 in stored blood.
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.
Frake
Paul C
PC
George Washington University School of Medicine, Washington, DC, USA.
Smith
Hadley E
HE
Chen
Lii-Fang
LF
Biffl
Walter L
WL
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
D020780:Matrix Metalloproteinase 9