Modulation of Neutrophil Function by Recombinant Human IgG1 Fc Hexamer in the Endogenous K/BxN Mouse Model of Rheumatoid Arthritis.

Introduction: Neutrophils are a pivotal cell type in the K/BxN mouse model of rheumatoid arthritis and play an essential role in the progression of the arthritis. They are readily activated by immune complexes (ICs) via their FcγRs to release IL-1β in addition to other cytokines, which are inducing cartilage destruction. Neutrophils also release neutrophil-active chemokines to recruit themselves in an autocrine manner to perpetuate tissue destruction.

(NZW × BXSB) F1 male mice: An unusual, severe and fatal mouse model of lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune/inflammatory disease. The heterogeneity and complexity of clinical presentation has made it challenging to study or treat this syndrome. The (NZW×BXSB) F1 lupus-prone male mouse model of this disease is potentially useful to study mechanism and treatment modalities, but there is a lack of information about this model's characterization and disease progression.

Red-blood-cell manufacturing methods and storage solutions differentially induce pulmonary cell activation.

Background And Objectives: Red-blood-cell (RBC) transfusion is associated with lung injury, which is further exacerbated by mechanical ventilation. Manufacturing methods of blood products differ globally and may play a role in the induction of pulmonary cell activation through alteration of the immunomodulatory property of the products. Here, the effect of different manufacturing methods on pulmonary cell activation was investigated in an in vitro model of mechanical ventilation.

Platelet vesicles are potent inflammatory mediators in red blood cell products and washing reduces the inflammatory phenotype.

Background: Studies suggest that washing red cell concentrates (RCCs) to remove soluble mediators and/or inflammatory components, such as extracellular vesicles (EVs), may lead to better clinical outcomes. This study tested the hypothesis that non-red blood cell (RBC) generated vesicles in RCC are potent inflammatory mediators in vitro and washing RCCs can reduce these vesicles and subsequently decrease the inflammatory activity of RCCs.

Study Design And Methods: Sixteen RCCs were pooled and split into four groups based on pre-wash storage time (Day 2 or 14; n = 4/group).

Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity.

Transfusion of red cell concentrates (RCCs) is associated with increased risk of adverse outcomes that may be affected by different blood manufacturing methods and the presence of extracellular vesicles (EVs). We investigated the effect of different manufacturing methods on hemolysis, residual cells, cell-derived EVs, and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived (AD), and whole blood-derived (WBD) methods were examined (n = 8 per method).

Screening of red blood cells for extracellular vesicle content as a product quality indicator.

Background: The controversy around the quality and clinical impact of stored and differentially manufactured red cell concentrates (RCCs) from different donor groups is ongoing. Current studies are limited by the lack of quality measures suitable for routine screening of RCCs. As extracellular vesicles (EVs) are markers of cellular activation or degradation, this study investigated the utility of EV screening to characterize the effects of RBCs production methods and storage.

Characteristics of Extracellular Vesicles in Red Blood Concentrates Change with Storage Time and Blood Manufacturing Method.

Background: Extracellular vesicles (EVs) in blood products are potential effectors of inflammation and coagulation after transfusion. The aim of this study was to assess the impact of different blood manufacturing methods and duration of hypothermic storage on the EV subpopulations in relation to other in vitro quality parameters of red blood cell concentrate (RCC) products.

Methods: RCCs were produced using whole blood filtration (WBF) or red cell filtration (RCF) (n = 12/method), refrigerated for 43 days, and evaluated for EV size profile and concentration, red cell deformability, ATP and 2,3-DPG, hemolysis, and hematological indices.

Extracellular vesicle characteristics in stored red blood cell concentrates are influenced by the method of detection.

Extracellular vesicles (EVs), including microvesicles and exosomes, are small phospholipid vesicles (≤1μm in diameter) that are present in blood products, accumulate during storage, and have a potential transfusion-related immunomodulatory role. Knowledge of EVs in stored blood products is limited due to the challenges and difficulties in detecting these heterogeneous submicron-sized vesicles. The aim of this study was to assess the impact of different approaches to characterize EVs in stored RBC products.

Impact of technical and assay variation on reporting of hemolysis in stored red blood cell products.

Background: Hemolysis of RBCs is an important measure of product quality and is influenced by donor factors, blood component manufacturing and storage. Percent hemolysis is determined using hematocrit (Hct), supernatant Hb (SHb) and total Hb (THb), each of which can be measured using a variety of methods.

Methods: Sixteen members of an international collaborative were surveyed to understand equipment and procedural variation in hemolysis testing.

Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing.

There is an emerging interest in the risks posed by the ability of blood transfusion to modulate the immune system of recipients. Observational trials suggest that RBC transfusions may be associated with increased morbidity and mortality, however studies demonstrating the deleterious consequences of transfusion-related immunomodulation have had conflicting results. Efforts to understand the biological mechanisms responsible for TRIM are under way, and are focusing on the role that the extracellular vesicles (EVs) that accumulate in a red cell concentrate (RCC) during storage may play.

The effects of rejuvenation during hypothermic storage on red blood cell membrane remodeling.

Background: Our previous studies showed that hypothermic storage (HS) induces red blood cell (RBC) microparticle (RMP) generation and changes in phosphatidylserine (PS) and CD47 expression on RBCs and RMPs. The aim of this study was to evaluate the effect of cold rejuvenation treatment at multiple time points during storage on these prehemolytic indicators of RBC membrane storage lesion.

Study Design And Methods: Leukoreduced RBC units in saline-adenine-glucose-mannitol were used to generate three groups: untreated controls, sham-treated units, and units treated with a cold (1-6°C) rejuvenation solution on Day 28, 35, or 42 of HS.

Storage of red blood cells affects membrane composition, microvesiculation, and in vitro quality.

Background: During storage detrimental biochemical and biomechanical changes occur within a red blood cell (RBC). RBC microparticles (RMPs) produced during storage have been identified as biomarkers of RBC quality, being potentially immunogenic and inhibitory to nitric oxide regulation.

Study Design And Methods: In this study, microvesiculation and changes in the composition of the RBC membrane were investigated throughout 49 days of storage and were correlated with in vitro assays examining membrane quality.