Abstract
Red blood cells (RBCs) passing through heart pumps, prosthetic heart valves and other cardiovascular devices undergo early senescence attributed to non-physiologic forces. We hypothesized that mechanical trauma accelerates aging by deformation of membrane proteins to cause binding of naturally occurring IgG. RBCs isolated from blood of healthy volunteers were exposed to high shear stress in a viscometer or microfluidics channel to mimic mechanical trauma and then incubated with autologous plasma. Increased binding of IgG was observed indicating forces caused conformational changes in a membrane protein exposing an epitope(s), probably the senescent cell antigen of band 3. The binding of immunoglobulin suggests it plays a role in the premature sequestration and phagocytosis of RBCs in the spleen. Measurement of IgG holds promise as a marker foreshadowing complications in cardiovascular patients and as a means to improve the design of medical devices in which RBCs are susceptible to sublethal trauma.
Highlights
Shear stress is important in the initiation and progression of certain pathologies
We considered that mechanisms for physiologic elimination of old Red blood cells (RBCs) might offer insights into the pathology of mechanical trauma
We have shown that binding of autologous immunoglobulin G(IgG) to RBCs occurs at exposure times and stress levels found in cardiovascular devices and conclude that it may be a contributing factor to premature removal of red blood cells in patients with these devices
Summary
Shear stress is important in the initiation and progression of certain pathologies. The high shear environment in ventricular assist devices (VADs) has been linked to markedly abridged circulatory lifespans for RBCs19. This is important because accelerated removal contributes to anemia for an individual and/or means an added metabolic load to replace the lost cells. Mean RBC lifespans for patients on continuous flow left ventricular assist devices have been reported to be as low as 30 days[19] This premature elimination of cells after blood trauma indicates more subtle, sublethal forms of damage may be involved and hints at underlying mechanisms similar to those effecting removal of the senescent RBC. One theory for aging involves attachment of methemoglobin to the interior surface of the RBC membrane or other stimulus to promote aggregation of the integral structural transmembrane protein band 3 (SLC4A1, a solute carrier family 4, anion exchanger, member 1)[33,34]; according to this theory, subsequent binding of naturally occurring antibodies(NAbs) to these band 3 clusters promotes capture of the cell in the spleen[35]
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