Abstract
Many factors in the surrounding environment have been reported to influence erythrocyte deformability. It is likely that some influences represent reversible changes in erythrocyte rigidity that may be involved in physiological regulation, while others represent the early stages of eryptosis, i.e., the red cell self-programmed death. For example, erythrocyte rigidification during exercise is probably a reversible physiological mechanism, while the alterations of red blood cells (RBCs) observed in pathological conditions (inflammation, type 2 diabetes, and sickle-cell disease) are more likely to lead to eryptosis. The splenic clearance of rigid erythrocytes is the major regulator of RBC deformability. The physicochemical characteristics of the surrounding environment (thermal injury, pH, osmolality, oxidative stress, and plasma protein profile) also play a major role. However, there are many other factors that influence RBC deformability and eryptosis. In this comprehensive review, we discuss the various elements and circulating molecules that might influence RBCs and modify their deformability: purinergic signaling, gasotransmitters such as nitric oxide (NO), divalent cations (magnesium, zinc, and Fe2+), lactate, ketone bodies, blood lipids, and several circulating hormones. Meal composition (caloric and carbohydrate intake) also modifies RBC deformability. Therefore, RBC deformability appears to be under the influence of many factors. This suggests that several homeostatic regulatory loops adapt the red cell rigidity to the physiological conditions in order to cope with the need for oxygen or fuel delivery to tissues. Furthermore, many conditions appear to irreversibly damage red cells, resulting in their destruction and removal from the blood. These two categories of modifications to erythrocyte deformability should thus be differentiated.
Highlights
It is logical to hypothesize that the receptor-mediated alterations in erythrocyte deformability induced by chemical messengers that physiologically circulate in the blood are reversible adaptative processes that do not involve eryptosis
We reported that leptin was correlated with plasma viscosity and erythrocyte disaggregation [163], and more recently, we confirmed that it was closely associated with increased red cell deformability and aggregation [164]
Various circulating and dysregulated inflammatory coagulation biomarkers, including fibrin(ogen), D-dimer, P-selectin, the von Willebrand Factor (VWF), C-reactive protein (CRP), and various cytokines directly bind to endothelial receptors and are likely to be indicative of a poor prognosis [240,241,242,243]
Summary
Red blood cells (RBCs) are known to markedly modify their shape in order to transit into small capillary vessels, whose radius is smaller than their own [1] This ability to deform results in RBC elongation in flow. After the RBCs were deformed under the influence of this shear stress, the dynamic RBC recovery was monitored and analyzed according to the Kelvin–Voigt model, allowing the measurement of an elastic shear modulus of RBCs submitted to different shear rates Even more recently, another group [7,8,9] developed a microfluidic impedance red cell assay (MIRCA) in order to measure. The same team further described the complexity of the mechanisms involved in these transition processes from one shape to another under the influence of an increase in shear stress [11] All this recent literature emphasizes the complexity of red cell deformation, which is far from a simple phenomenon. This paper is an attempt to summarize this large body of literature and to integrate our knowledge with regards to the classical definitions of deformability and eryptosis
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