title: Supernatant of stored platelets causes lung inflammation and coagulopathy in a novel in vivo transfusion model.
abstract: Transfusion-related acute lung injury is suggested to be a "2-hit" event resulting from priming and activation of pulmonary neutrophils. Activation may result from infusion of lysophosphatidylcholines (LysoPCs), which accumulate during storage of blood products. In the present study, we developed a syngeneic in vivo transfusion model to test whether storage of platelet concentrates (PLTs) results in lung injury in healthy rats as well as in a "2-hit" model using lipopolysaccharide-pretreated rats. In addition, the effect of washing of platelets was studied. In healthy rats, transfusion of aged PLTs caused mild lung inflammation. In LPS-pretreated rats, transfusion of aged PLTs, but not fresh PLTs, augmented pulmonary systemic coagulopathy. When PLTs components were transfused separately, supernatant of aged PLTs, but not washed aged platelets, induced pulmonary injury in the "2-hit" model. Supernatants of aged PLTs contained increased concentrations of LysoPCs compared with fresh PLTs, which enhanced neutrophil priming activity in vitro. We conclude that transfusion of aged PLTs induces lung inflammation in healthy rats. In a "2-hit" model, aged PLTs contribute to pulmonary and systemic coagulopathy, which may be mediated by LysoPCs, which accumulate in the supernatant of PLTs during storage.
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Center, Amsterdam. a.p.vlaar@amc.uva.nl
authors.forename: Alexander P J
authors.initials: AP
authors.lastname: Vlaar
authors.forename: Jorrit J
authors.initials: JJ
authors.lastname: Hofstra
authors.forename: Wim
authors.initials: W
authors.lastname: Kulik
authors.forename: Henk
authors.initials: H
authors.lastname: van Lenthe
authors.forename: Rienk
authors.initials: R
authors.lastname: Nieuwland
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Levi
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Anton T J
authors.initials: AT
authors.lastname: Tool
authors.forename: Dirk
authors.initials: D
authors.lastname: de Korte
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Juffermans
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000473:pathology; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005342:Fibrinolysis; D006801:Humans; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013048:Specimen Handling; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D065227:Transfusion Reaction
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines