Changes in donor leukocytes during blood storage. Implications on post-transfusion immunomodulation and transfusion-associated GVHD.
Freshly drawn peripheral blood granulocytes, monocytes and NK cells express Fas-L following activation. Fully functional soluble Fas-L (sFas-L) is released and found in fresh plasma samples from healthy volunteers coupled to a Fas-L binding factor (PFBF). In the absence of plasma leukocytes undergo rapid apoptosis with 15% of the granulocytes and 25% of the monocytes showing signs of apoptosis immediately following separation. Apoptosis progresses during refrigerated storage even in the presence of plasma and all granulocytes disintegrate by day 15 of storage. The absence of plasma increases the rate of apoptosis. The resulting increased expression of PS on apoptosing leukocytes enhances blood procoagulant activity. Whereas transfusions of fresh blood lead to alloimmunization, the functional impairment and death of antigen-presenting cells during storage eliminates their ability to stimulate cytotoxic immune responses. Additionally, loss of function and death of donor T cells during storage preclude the possibility for development of post-transfusion GVHD. Continued storage leads to the secondary necrosis of apoptosed leukocytes and the release of soluble antigens. Depending on dose, transfusion of such products may lead to immunosuppression due to a T2 bias of the immune response.
Mincheff
M
M
Transfusion and Cryopreservation Research Program, NMRI, Naval Medical Center, Bethesda, MD 20889-5607, USA.
D017209:Apoptosis; D001793:Blood Preservation; D002463:Cell Membrane Permeability; D002470:Cell Survival; D053222:Fas Ligand Protein; D006086:Graft vs Host Disease / Q000209:etiology*; D006648:Histocompatibility; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007962:Leukocytes / Q000166:cytology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000097:blood; D010949:Plasma / Q000502:physiology; D013997:Time Factors; D065227:Transfusion Reaction
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins