PEN110 treatment functionally inactivates the PBMNCs present in RBC units: comparison to the effects of exposure to gamma irradiation.
BACKGROUND
The presence of WBCs in blood components is the major factor influencing the immunologic consequences of transfusion. Attempts to ameliorate these responses have used WBC reduction or inactivation by ionizing radiation. PEN110 (Inactine, V. I. Technologies) is a chemical that inhibits the replication of infectious pathogens by modifying their nucleic acids. These experiments compared effects of PEN110 treatment or gamma irradiation on WBC function.


METHODS
Aliquots of non-WBC-reduced RBC units were treated with PEN110 or gamma irradiation with appropriate controls, and PBMNCs from these units were tested with in vitro assays. The assays included immunophenotyping, activating T cells with phorbol ester, proliferation of cells in response to mitogens or allogeneic cells, and determining the ability of cells to stimulate proliferative responses and to produce IL-8. DNA fragmentation following PEN110 treatment was examined by PCR and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assays.


RESULTS
Treatment of non-WBC-reduced RBC units with PEN110 functionally inactivated WBC in all in vitro assays used. In contrast, while gamma irradiation inhibited proliferation of the WBCs, it did not or only partially inhibited the ability of WBC to function in the other assays. PEN110, but not gamma irradiation, rapidly induced fragmentation of cellular DNA.


CONCLUSIONS
Because PEN110 was as effective as gamma irradiation at inhibiting WBC proliferation, PEN110 treatment could potentially be used to prevent the development of GVHD following transfusion.
Fast
Loren D
LD
Department of Medicine, Division of Hematology and Oncology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA. Loren_Fast@brown.edu
DiLeone
Gilbert
G
Edson
Clark M
CM
Purmal
Andrei
A
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002455:Cell Division; D053938:DNA Fragmentation; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D005720:Gamma Rays; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D011073:Polyamines / Q000494:pharmacology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016209:Interleukin-8; D037181:Lectins, C-Type; D011073:Polyamines; D000099192:CD69 Antigens; C451719:PEN 110