Erythrocyte aging: a more than superficial resemblance to apoptosis?

Contains fulltext : 47441.pdf (publisher's version ) (Open Access)In physiological circumstances, erythrocyte aging leads to binding of autologous IgG followed by recognition and removal through phagocytosis, mainly by Kupffer cells in the liver. This process is triggered by the appearance of a senescent erythrocyte-specific antigen. The functional and structural characteristics of senescent erythrocytes strongly suggest that this antigen originates on band 3, probably by calcium-induced proteolysis. Generation of vesicles enriched in denatured hemoglobin is an integral part of the erythrocyte aging process. These vesicles are also removed by Kupffer cells, with a major role for exposure of phosphatidylserine. Moreover, senescent erythrocyte-specific antigens are present on vesicles. Thus, vesicles and senescent erythrocytes may be recognized and removed through the same signals. These and other, recent data support the theory that erythrocyte aging is a form of apoptosis that is concentrated in the cell membrane, and provide the context for future studies on initiation and regulation of the erythrocyte aging process. Insight into the normal aging mechanism is essential for understanding the fate of erythrocytes in pathological circumstances and the survival of donor erythrocytes after transfusion

DETERMINANTS OF RED-BLOOD-CELL DEFORMABILITY IN RELATION TO CELL AGE

Red blood cell (RBC) deformability was determined with an ektacytometer in fractions separated on the basis of differences in cell volume or density. Deformability was measured with ektacytometry (rpm-scan and osmo-scan). We studied three groups of RBC fractions:l. By counterflow centrifugation we obtained fractions of different cell age which showed a slight decrease in mean corpuscular haemoglobin concentration (MCHC) and an increase in surface-to-volume (S/V) ratio in fractions with older cells. 2. By Percoll fractionation fractions were obtained which showed a pronounced increase in (MCHC) but no change in S/V ratio. 3. By a combination of both fractionation techniques, fractions were obtained which showed an increased MCHC and an increase in S/V ratio. Deformability in group 1,2 and 3 showed respectively no change, a moderate decrease and a pronounced decrease in fractions of older cells. A decline in deformability occurs during the aging process of the red blood cell. This decline in deformability in old red cells is greater than originally thought. This decline is the result of an increase in haemoglobin concentration and a second factor, probably a decrease in membrane elasticity.</p

DETERMINANTS OF RED-BLOOD-CELL DEFORMABILITY IN RELATION TO CELL AGE

Red blood cell (RBC) deformability was determined with an ektacytometer in fractions separated on the basis of differences in cell volume or density. Deformability was measured with ektacytometry (rpm-scan and osmo-scan). We studied three groups of RBC fractions:l. By counterflow centrifugation we obtained fractions of different cell age which showed a slight decrease in mean corpuscular haemoglobin concentration (MCHC) and an increase in surface-to-volume (S/V) ratio in fractions with older cells. 2. By Percoll fractionation fractions were obtained which showed a pronounced increase in (MCHC) but no change in S/V ratio. 3. By a combination of both fractionation techniques, fractions were obtained which showed an increased MCHC and an increase in S/V ratio. Deformability in group 1,2 and 3 showed respectively no change, a moderate decrease and a pronounced decrease in fractions of older cells. A decline in deformability occurs during the aging process of the red blood cell. This decline in deformability in old red cells is greater than originally thought. This decline is the result of an increase in haemoglobin concentration and a second factor, probably a decrease in membrane elasticity

YOUNG RED-BLOOD-CELLS - OBSERVATIONS ABOUT THE CYTOMETRIC AND MORPHOLOGIC ALTERATIONS IN THE BEGINNING OF THEIR LIFE

A recently described separation technique consisting of a combination of counterflow centrifugation and subsequent density (Percoll) separation was tested for its ability to enrich red cell populations with young cells in comparison to either separation technique alone. The relative age of every fraction was determined by HbAlc measurements, resulting in the lowest HbAlc for the combination method. Conventional reticulocyte counting and flowcytometric counting with thiazole orange indicated that in the youngest fractions the combination method showed the highest reticulocyte counts. There was a good correlation between manual and flowcytometric counting results. Radio-iron studies showed a two-fold enrichment with young cells in the fraction with the lowest HbAlc acquired by the combination technique in comparison to the other two methods. Cytometric measurements showed that the fractions with the lowest HbAlc were the ones with the highest MCV and MCH and the lowest MCHC. Besides loss of their RNA-material, young cells already seem to loose water and haemoglobin like older cells, resulting in a decrease of MCV and MCH and in increase in MCHC. It is concluded that combining counterflow centrifugation with subsequent density fractionation results in superior enrichment with young cells in comparison to the results of each method alone