A Flow Induced Autoimmune Response and Accelerated Senescence of Red Blood Cells in Cardiovascular Devices

Buerck, James P.; Burke, Dustin K.; Schmidtke, David W.; Snyder, Trevor A.; Papavassiliou, Dimitrios V.; O’Rear, Edgar A.

doi:10.1038/s41598-019-55924-y

Cited by 17 publications

(18 citation statements)

References 55 publications

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“…Several well-known methods have been established to examine the effect of shear stresses on cells. These include viscometers used to apply uniform levels of shear stress to suspensions and rectangular microfluidic channels [ 21 , 22 , 23 ]. Devices used for observing cells under extensional flow also exist with several options for the bioscientist or bioengineer wanting to study the effects of elongational flow on cells, as will be discussed below and summarized in Table 1 .…”

Section: Experimental Methods For Extensional Stresses On Cellsmentioning

confidence: 99%

Elongational Stresses and Cells

Foster

Papavassiliou

O’Rear

2021

Cells

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Fluid forces and their effects on cells have been researched for quite some time, especially in the realm of biology and medicine. Shear forces have been the primary emphasis, often attributed as being the main source of cell deformation/damage in devices like prosthetic heart valves and artificial organs. Less well understood and studied are extensional stresses which are often found in such devices, in bioreactors, and in normal blood circulation. Several microfluidic channels utilizing hyperbolic, abrupt, or tapered constrictions and cross-flow geometries, have been used to isolate the effects of extensional flow. Under such flow cell deformations, erythrocytes, leukocytes, and a variety of other cell types have been examined. Results suggest that extensional stresses cause larger deformation than shear stresses of the same magnitude. This has further implications in assessing cell injury from mechanical forces in artificial organs and bioreactors. The cells’ greater sensitivity to extensional stress has found utility in mechanophenotyping devices, which have been successfully used to identify pathologies that affect cell deformability. Further application outside of biology includes disrupting cells for increased food product stability and harvesting macromolecules for biofuel. The effects of extensional stresses on cells remains an area meriting further study.

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Section: Experimental Methods For Extensional Stresses On Cellsmentioning

confidence: 99%

Elongational Stresses and Cells

Foster

Papavassiliou

O’Rear

2021

Cells

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“…A study by Buerck et al pointed out the importance of shear stress in the induction and progression of the autoimmune response and accelerated senescence of RBC [56]. Their results showed increased binding of IgG to the RBC membrane exposed to high shear stress, indicating conformational changes in the RBC membrane protein, most probably the senescent antigen of band 3, thus exposing epitopes to naturally occurring antibodies (Fig.…”

Section: Pathogenesis Of Aihamentioning

confidence: 95%

Autoimmune hemolytic anemia: current knowledge and perspectives

et al. 2020

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Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.

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“…These effects have a significant dependence upon metabolic alterations, which are uniquely elicited by different stressors including nutrient depletion, Ca 2+ overload, and hyperthermia [ 18 ]. The onset of eryptosis is associated with the release of microparticles (MPs), membrane-bound vesicles 0.1–1 μm in diameter, which can also be influenced by increased shear stress [ 19 , 20 , 21 ]. Although shear stress and oxidative stress are both elevated during exercise, previous studies have indicated that short maximal exercise tests do not cause RBC-MPs or markers of eryptosis to increase [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling

Nemkov

Skinner

Nader

et al. 2021

IJMS

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Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.

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A Flow Induced Autoimmune Response and Accelerated Senescence of Red Blood Cells in Cardiovascular Devices

Cited by 17 publications

References 55 publications

Elongational Stresses and Cells

Elongational Stresses and Cells

Autoimmune hemolytic anemia: current knowledge and perspectives

Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling

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