Browsing by Author "Burns, Jennie M."
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Item Deterioration of red blood cell mechanical properties is reduced in anaerobic storage(Blood Transfusion, 1/14/2016) Burns, Jennie M.; Yoshida, Tatsuro; Dumont, Larry J.; Yang, Xiaoxi; Piety, Nathaniel Z.; Shevkoplyas, Sergey S.Background Hypothermic storage of red blood cells (RBCs) results in progressive deterioration of the rheological properties of the cells, which may reduce the efficacy of RBC transfusions. Recent studies have suggested that storing RBC units under anaerobic conditions may reduce this storage-induced deterioration. Materials and methods The aim of this study was to compare the rheological properties of conventionally and anaerobically stored RBC and provide a measure of the relationship between oxidative damage to stored RBC and their ability to perfuse microvascular networks. Three different microfluidic devices were used to measure the ability of both types of stored RBC to perfuse artificial microvascular networks. Flow rates of the RBC passing through the entire network (bulk perfusion) and the individual capillaries (capillary perfusion) of the devices were measured on days 2, 21, 42, and 63 of storage. Results The bulk perfusion rates for anaerobically stored RBC were significantly higher than for conventionally stored RBCs over the entire duration of storage for all devices (up to 10% on day 42; up to 14% on day 63). Capillary perfusion rates suggested that anaerobically stored RBC units contained significantly fewer non-deformable RBC capable of transiently plugging microfluidic device capillaries. The number of plugging events caused by these non-deformable RBC increased over the 63 days of hypothermic storage by nearly 16- to 21-fold for conventionally stored units, and by only about 3- to 6-fold for anaerobically stored units. Discussion The perfusion measurements suggest that anaerobically stored RBC retain a greater ability to perfuse networks of artificial capillaries compared to conventionally (aerobically) stored RBC. It is likely that anaerobic storage confers this positive effect on the bulk mechanical properties of stored RBC by significantly reducing the number of non-deformable cells present in the overall population of relatively well-preserved RBC.Item SLE serum deposits C4d on red blood cells, decreases red blood cell membrane deformability, and promotes nitric oxide production(Arthritis & Rheumatism, 4/23/2012) Ghiran, Ionita C.; Zeidel, Mark L.; Shevkoplyas, Sergey S.; Burns, Jennie M.; Tsokos, George C.; Kyttaris, Vasileios C.Objective Systemic lupus erythematosus (SLE) is characterized by intravascular activation of the complement system and deposition of complement fragments (C3 and C4) on plasma membranes of circulating cells, including red blood cells (RBC). The aim of this study was to address whether this process affects the biophysical properties of RBC. Methods Serum and red blood cells were isolated from patients with SLE, and healthy controls. RBC from healthy O Rh negative individuals were incubated with SLE or control serum. We used flow cytometry to assess complement fragment deposition on RBC. RBC membrane deformability was measured using 2D microchannel arrays. Protein phosphorylation levels were quantified by western blot. Results Incubation of healthy donor RBC with sera from patients with SLE but not control sera led to deposition of C4 fragments on the RBC. Complement decorated RBC exhibited significant decrease in both membrane deformability and flickering. Sera from SLE patients triggered a transitory Ca++ influx in RBC that was associated with decreased phosphorylation of ?-spectrin, and increased phosphorylation of band 3, two key proteins of RBC cytoskeleton. Finally, SLE but not control sera led to the production of nitric oxide (NO) by RBC. Conclusion Our data suggest that complement activation in patients with SLE leads to calcium dependent cytosketeletal changes in RBC that render them less deformable, likely impairing their flow through capillaries. This phenomenon may negatively impact the delivery of oxygen to the tissues.