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Abstract
Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell clearance mechanism(s) are expression of neoantigens on red cell surface, exposure phosphatidylserine and decreased deformability. While there is some correlation between these changes with aging their causal role for red cell clearance has not been established. Despite plethora of investigations, we still have incomplete understanding of the molecular details of red cell clearance. In this review, we have reviewed the recent data on clearance of senescent red cells. We anticipate recent progresses in in vivo red cell labeling and the explosion of modern proteomic techniques will, in near future, facilitate our understanding of red cell senescence and their destruction.
Highlights
Under normal physiological condition, red cell concentration is maintained at a relatively constant value of ∼5 million per μL (4.52–5.90 in men and 4.10–5.10 in women) by equilibration of production and destruction
The red cells have robust redox mechanisms to quench the reactive oxygen species (ROS) and protect the hemoglobin and other components including membrane proteins, lipids, and cytoplasmic components from injury. To repair this damage and to allow oxygen to bind to hemoglobin, red cells metabolism must generate reduced nicotinamide adenine dinucleotide phosphate (NADPH) for antioxidant protection mediated principally by glucose-6-phosphate dehydrogenase (G6PD) activity
While the spleen is essential for remodeling of erythrocytes and clearing of defective red cells, more needs to be learned about splenic contribution to physiological clearance of senescent erythrocytes
Summary
Under normal physiological condition, red cell concentration is maintained at a relatively constant value of ∼5 million per μL (4.52–5.90 in men and 4.10–5.10 in women) by equilibration of production and destruction. The red cells have robust redox mechanisms to quench the ROS and protect the hemoglobin and other components including membrane proteins, lipids, and cytoplasmic components from injury To repair this damage and to allow oxygen to bind to hemoglobin, red cells metabolism must generate reduced nicotinamide adenine dinucleotide phosphate (NADPH) for antioxidant protection mediated principally by glucose-6-phosphate dehydrogenase (G6PD) activity. While the spleen is essential for remodeling of erythrocytes and clearing of defective red cells, more needs to be learned about splenic contribution to physiological clearance of senescent erythrocytes. It is very likely there are other sites for senescent red blood cell clearance
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