Abstract
Most blood transfusion-related adverse reactions involve the immunologic responses of recipients to exogenous blood components. Extracellular vesicles isolated from packed red cells can affect the recipient’s immune system. Mast cells are traditionally known as effector cells for allergic transfusion reactions. However, growing evidence supports the notion that activated mast cells might disturb host innate immunologic responses. Exosomes are a type of extracellular vesicle. To determine the effect of exosomes on mast cells, we enriched exosomes derived from volunteer plasma (EXs-nor) and packed red cells (EXs-RBCs) using ultracentrifugation and incubated them with a human mast cell line (HMC-1). We found that EXs-RBC exposure increased the expression of tryptase-1 and prostaglandin D2, the production of multiple inflammatory mediators, and the levels of Toll-like receptor-3 (TLR-3) and phospho-mitogen-activated protein kinase (MAPK) in HMC-1 cells. MAPK inhibitors (SB203580, PD98059, and SP600125) and a TLR-3/dsRNA complex inhibitor reduced the EXs-RBC-stimulated production of inflammatory mediators in HMC-1 cells, whereas the TLR-3 agonist [poly (A:U)] elevated the production of these mediators. These results indicate that EXs-RBCs activate HMC-1 cells and elicit the production of multiple inflammatory mediators, partly via the TLR-3 and MAPK pathways. Mast cells activated by EXs-RBCs exhibit complex inflammatory properties and might play a potential role in transfusion-related adverse reactions.
Highlights
Blood transfusion is an essential therapeutic method in clinical practice, and packed red cell (RBC) transfusion is the primary blood transfusion administration used to treat hemorrhage and improve tissue oxygenation [1]
We focused on the expression of mast cell activated markers, tryptase-1 and prostaglandin D2 (PGD-2), the inflammatory pattern of HMC-1 cells responding to EXs-RBCs, and the activation of Toll-like receptor-3 (TLR-3) and mitogen-activated protein kinase (MAPK) pathways
CCK-8 assay results showed no significant change in HMC-1 cell viability after treatment for 24 h (p > 0.05, data not shown), indicating that the experimental outcomes were not associated with HMC-1 cell viability under various challenges
Summary
Blood transfusion is an essential therapeutic method in clinical practice, and packed red cell (RBC) transfusion is the primary blood transfusion administration used to treat hemorrhage and improve tissue oxygenation [1]. RBC transfusion is lifesaving, it is associated with many transfusion-related adverse reactions [2], most of which involve immunologic responses of recipients to exogenous blood components. The blood components that attack the recipient’s immune response and the underlying mechanism of this process are mostly unknown. The potential immunologic effect of extracellular vesicles from RBCs has attracted growing interest [3]. Extracellular vesicles are small double-membrane vesicles that can be secreted by RBCs and increase in number with storage time. Exosomes (EXs), a type of extracellular vesicle with a diameter ranging between 30 and 150 nm, contain RNA, DNA, and protein, which might participate in many critical physiological and pathological processes [8]
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