Effects of Aging on Antioxidant Response and Phagocytosis in Senescent Erythrocytes

Abstract

Red blood cell (RBC) aging is a complex process affected by immunological and biochemical parameters. In this work we studied the antioxidant response in RBC of different ages. We also investigated their interaction with peripheral blood monocytes. Anticoagulated blood samples from 19 O RhD+ volunteers' donors were processed. Young (Y) RBC and Senescent (Se) RBC were obtained by self-formed gradients of Percoll. The fractionation of the erythrocytes suspensions was demonstrated by statistically significant density-related changes in hematological determinations. Activities of glucose-6-phosphate dehydrogenase (G6PD), of soluble NADH-cytochrome b5 reductase (b5Rs) and membrane-bound b5R (b5Rm) were determined spectrophotometrically. The interaction between monocytes and different RBC suspensions was evaluated by the erythrophagocytosis assay. The G6PD and b5Rm activities in SeRBC were significantly lower than that observed in YRBC. No differences were found in the b5Rs of both groups. We observed an increased rate of erythrophagocytosis the SeRBC compared to YRBC. The decline in the activities of G6PD and b5Rm would indicate a decrease in the antioxidant response associated to RBC aging. These findings would signify that the oxidative changes of membrane occurring during the life span of the RBC might be relevant in the process of removal of SeRBC from the circulation.

Longer storage of red blood cells is associated with increased in vitro erythrophagocytosis

“…Previous studies, using Percoll‐fractionated RBCs, have shown that denser RBCs are more susceptible to phagocytosis . In contrast, our results did not show a significant difference in erythrophagocytosis between density fractionated young and old stored RBCs (Fig.…”

“…). Targeting of RBCs for phagocytosis in vivo is complex and involves a number of different mechanisms that may contribute to the increased erythrophagocytosis observed in this study. We have previously shown that detection of RBC membrane sialylation using lectins decreases over the storage period .…”

“…CD47, sialic acid) and oxidative damage to membrane proteins. These changes, in turn, have been implicated in the exposure of band‐3, the cytoskeletal protein ankyrin, opsonization by naturally occurring antibodies or complement and changes to RBC membrane asymmetry leading to exposure of phosphatidylserine .…”

Protein Kinase CK1α Regulates Erythrocyte Survival

“…Thus, only a fraction of circulating erythrocytes appear to be sensitive to those challenges. The susceptibility may be influenced by erythrocyte age, as senescent erythrocytes may have a decreased capacity to counteract oxidative stress [45][46][47]. On the other hand, newly formed erythrocytes may by particularly vulnerable, as shown following return from high altitude or a space flight [48] or in patients with paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome [49].…”

Peroxyl-induced oxidative stress in aging erythrocytes of rat

“…Normal rat erythrocytes have a life span of 90 days, during which period cells senesce and are phagocytosed by macrophages. A normal senescent erythrocyte is identified by reduced activities of enzymes such as glucose-6-phosphate dehydrogenase and membrane-bound b5R (b5Rm) that are indicators of reduced antioxidant responses accompanying aging of erythrocytes (Brajovich et al 2009). However, under certain conditions, accelerated clearance of erythrocytes from circulation may occur with the problem being magnified by the low resistance of young erythrocytes towards various challenges Effect of peroxyl radical-mediated changes on intracellular calcium and in the presence and absence of vitamin C in young and old erythrocytes.…”