Red Blood Cells: Tethering, Vesiculation, and Disease in Micro-Vascular Flow

Abstract

The red blood cell has become implicated in the progression of a range of diseases; mechanisms by which red cells are involved appear to include the transport of inflammatory species via red cell-derived vesicles. We review this role of RBCs in diseases such as diabetes mellitus, sickle cell anemia, polycythemia vera, central retinal vein occlusion, Gaucher disease, atherosclerosis, and myeloproliferative neoplasms. We propose a possibly unifying, and novel, paradigm for the inducement of RBC vesiculation during vascular flow of red cells adhered to the vascular endothelium as well as to the red pulp of the spleen. Indeed, we review the evidence for this hypothesis that links physiological conditions favoring both vesiculation and enhanced RBC adhesion and demonstrate the veracity of this hypothesis by way of a specific example occurring in splenic flow which we argue has various renderings in a wide range of vascular flows, in particular microvascular flows. We provide a mechanistic basis for membrane loss and the formation of lysed red blood cells in the spleen that may mediate their turnover. Our detailed explanation for this example also makes clear what features of red cell deformability are involved in the vesiculation process and hence require quantification and a new form of quantitative indexing.

Advances in Microfluidics for Single Red Blood Cell Analysis

“…Nevertheless, the primary goal of microfluidic single RBC research remains in finding the most convenient ways to advance biological and analytical studies in application-specific systems, such as chemotaxic assays, low resource diagnosis, and rapid assessment of biofluids [433]. These microfluidics chips have been implemented and studied globally to gain performance factors [434] for Point-of-Care (POC) diagnosis applications [435] and cellular studies [436][437][438]. There is also a demand for non-destructive and label-free analytical techniques for the rapid detection of erythrocytes' pathologies and alterations on the molecular level, where Raman spectroscopy plays an important role [439].…”

Unexplored Roles of Erythrocytes in Atherothrombotic Stroke

“…However, erythrocyte-rich thrombi have been associated with favorable outcomes in patients being treated with mechanical thrombectomy [ 63 ]. Since erythrocyte vesiculation shreds CD47 from the erythrocyte surface [ 64 ], it would be interesting to examine the role of lipid metabolism on erythrocyte–fibrinogen interactions.…”

Advances in Diagnosis and Pathophysiology of Microvascular Dysfunction

“…Under pathophysiological conditions (e.g., diabetes, sickle cell anemia, and central retinal vein occlusion), structural and functional adaptations of microvascular networks and erythrocytes can be quantified using novel imaging technologies and advanced quantification metrics, such as multispectral and hyperspectral imaging and optical coherence tomography. Asaro and Cabrales [4] propose a novel paradigm to induce red blood cell (RBC) vesiculation during vascular flow of red blood cells adhering to the vascular endothelium and to the red pulp of the spleen. They hypothesize that erythrocytes can be driven to vesiculate by adhering to endothelial splenic slits via tether formation.…”

“…Using simulation results of red cell deformability in the vesiculation process, their synthesized findings provide a mechanistic basis for membrane loss and the formation of lysed RBCs in the spleen. Asaro and Cabrales [4] also discuss how various diseases and aging affect RBC adherence to endothelial cells, including diabetes, Gaucher disease, and myeloproliferative neoplasms. However, these mechanistic approaches using the combined RBC characteristics of deformability and adhesion allow for the early detection and diagnosis of diseases.…”