title: The immune-stimulation capacity of liposome-treated red blood cells.
abstract: Our in vivo studies on a rat model established safety of transfusing liposome-treated red blood cells (RBCs) but identified the potential for immune modulation as related to transfusion efficacy of liposome-treated RBCs. The aim of this study was at assessing the impact of liposome-induced membrane changes on the immune profile of liposome-treated RBCs by (a) evaluating their interaction with endothelial cells and monocytes; and (b) the resulting immune response derived from this interaction, in the form of cytokine release, adhesion molecules expression and phagocytosis. Unilamellar liposomes were synthesized to contain unsaturated phospholipids (1,2-dioleoyl-sn-glycero-3-phosphocholine [DOPC]:CHOL, 7:3 mol%). The human RBCs immune profile was assessed by incubating control and DOPC-treated RBCs with human umbilical vein endothelial cells (HUVECs) and monocytes. Cytokine release measured by Luminex technology, vascular cell adhesion molecule (VCAM)-1 and E-selectin on HUVECs measured by flow cytometry, and the erythrophagocytic activity of monocytes by monocyte monolayer assay (MMA) were determined. Fibroblast growth factor [FGF]-2 was the only cytokine released by HUVECs that remained increased after incubation with DOPC-treated RBCs compared to control throughout storage. The expression of both VCAM-1 (15.3 ± 5.6% versus 6.3 ± 0.9%, p = 0.008) and E-selectin (18.0 ± 6.3% versus 6.6 ± 0.7%, p = 0.004) by HUVECs were significantly increased after incubation with DOPC-treated RBCs at day 2 of storage. The MMA resulted in phagocytic indexes of zero for both control and DOPC-treated RBCs at day 2 and 42 of storage. The liposome treatment did not result in significant changes to the immune profile of stored DOPC-treated RBCs. These findings combined with previous in vivo results, make liposome treatment a potential candidate for application in RBC preservation and open the possibility for clinical use with other cell types.
authors.affiliation: a Canadian Blood Services Centre for Innovation , Edmonton , AB , Canada.|b Department of Laboratory Medicine and Pathology , University of Alberta , Edmonton , AB , Canada.
authors.forename: Luciana
authors.initials: L
authors.lastname: da Silveira Cavalcante
authors.affiliation: c Canadian Blood Services Centre for Innovation , Toronto , ON , Canada.|d Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , ON , Canada.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Branch
authors.affiliation: e The Hospital for Sick Children , Toronto , ON , Canada , and.
authors.forename: Trang T
authors.initials: TT
authors.lastname: Duong
authors.affiliation: e The Hospital for Sick Children , Toronto , ON , Canada , and.|f Department of Paediatrics , University of Toronto , Toronto , ON , Canada.
authors.forename: Rae S M
authors.initials: RSM
authors.lastname: Yeung
authors.affiliation: a Canadian Blood Services Centre for Innovation , Edmonton , AB , Canada.|b Department of Laboratory Medicine and Pathology , University of Alberta , Edmonton , AB , Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Acker
authors.affiliation: a Canadian Blood Services Centre for Innovation , Edmonton , AB , Canada.|b Department of Laboratory Medicine and Pathology , University of Alberta , Edmonton , AB , Canada.
authors.forename: Jelena L
authors.initials: JL
authors.lastname: Holovati
mesh_terms: D002784:Cholesterol / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000276:immunology*; D009000:Monocytes; D010587:Phagocytosis; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D019040:E-Selectin; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; C546936:SELE protein, human; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine
keywords: Cytokines; HUVECs; liposomes; monocytes; red blood cells