Aged Human Stored Red Blood Cell Supernatant Inhibits Macrophage Phagocytosis in an HMGB1 Dependent Manner After Trauma in a Murine Model. Shock 2017 Feb;47(2):217-224
Date
08/05/2016Pubmed ID
27488090Pubmed Central ID
PMC5235959DOI
10.1097/SHK.0000000000000716Scopus ID
2-s2.0-84980340113 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Red blood cell transfusions in the setting of trauma are a double-edged sword, as it is a necessary component for life-sustaining treatment in massive hemorrhagic shock, but also associated with increased risk for nosocomial infections and immune suppression. The mechanisms surrounding this immune suppression are unclear. Using supernatant from human packed red blood cell (RBC), we demonstrate that clearance of Escherichia coli by macrophages is inhibited both in vitro and in vivo using a murine model of trauma and hemorrhagic shock. We further explore the mechanism of this inhibition by demonstrating that human-stored RBCs contain soluble high-mobility group box 1 protein (HMGB1) that increases throughout storage. HMGB1 derived from the supernatant of human-stored RBCs was shown to inhibit bacterial clearance, as neutralizing antibodies to HMGB1 restored the ability of macrophages to clear bacteria. These findings demonstrate that extracellular HMGB1 within stored RBCs could be one factor leading to immune suppression following transfusion in the trauma setting.
Author List
Zettel KR, Dyer M, Raval JS, Wu X, Klune JR, Gutierrez A, Triulzi DJ, Billiar TR, Neal MDAuthor
Mitchell R. Dyer MD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDisease Models, Animal
Erythrocytes
Escherichia coli
HMGB1 Protein
Humans
Macrophages
Male
Mice
Mice, Inbred C57BL
Phagocytosis
Shock, Hemorrhagic
Wounds and Injuries
