title: Transfusion of Human Platelets Treated with Mirasol Pathogen Reduction Technology Does Not Induce Acute Lung Injury in Mice.
abstract: Pathogen reduction technology (PRT) has been developed in an effort to make the blood supply safer, but there is controversy as to whether it may induce structural or functional changes to platelets that could lead to acute lung injury after transfusion. In this study, we used a commercial PRT system to treat human platelets that were then transfused into immunodeficient mice, and the development of acute lung injury was determined. P-selectin expression was higher in the Mirasol PRT-treated platelets compared to control platelets on storage day 5, but not storage day 1. Transfusion of control vs. Mirasol PRT-treated platelets (day 5 of storage, 109 platelets per mouse) into NOD/SCID mice did not result in lung injury, however transfusion of storage day 5 platelets treated with thrombin receptor-activating peptide increased both extravascular lung water and lung vascular permeability. Transfusion of day 1 platelets did not produce lung injury in any group, and LPS priming 24 hours before transfusion had no effect on lung injury. In a model of transfusion-related acute lung injury, NOD/SCID mice were susceptible to acute lung injury when challenged with H-2Kd monoclonal antibody vs. isotype control antibody. Using lung intravital microscopy, we did not detect a difference in the dynamic retention of platelets in the lung circulation in control vs. Mirasol PRT-treated groups. In conclusion, Mirasol PRT produced an increase in P-selectin expression that is storage-dependent, but transfusion of human platelets treated with Mirasol PRT into immunodeficient mice did not result in greater platelet retention in the lungs or the development of acute lung injury.
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Axelle
authors.initials: A
authors.lastname: Caudrillier
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Beñat
authors.initials: B
authors.lastname: Mallavia
authors.affiliation: Terumo BCT, Inc., Lakewood, Colorado, United States of America.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Rouse
authors.affiliation: Terumo BCT, Inc., Lakewood, Colorado, United States of America.
authors.forename: Susanne
authors.initials: S
authors.lastname: Marschner
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America; Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Looney
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology*; D000818:Animals; D001792:Blood Platelets / Q000166:cytology; D001793:Blood Preservation; D058731:Blood Safety; D002199:Capillary Permeability; D005434:Flow Cytometry; D006801:Humans; D000069416:Intravital Microscopy; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D017319:Photosensitizing Agents / Q000737:chemistry*; D017713:Platelet Transfusion; D012256:Riboflavin / Q000737:chemistry
chemical_list: D019007:P-Selectin; D010446:Peptide Fragments; D017319:Photosensitizing Agents; C076901:thrombin receptor-activating peptide (P508-530); D012256:Riboflavin