Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro

Abstract

The online version of this article has a Supplementary Appendix. BackgroundThe lifespan of red blood cells is terminated when macrophages remove senescent red blood cells by erythrophagocytosis. This puts macrophages at the center of systemic iron recycling in addition to their functions in tissue remodeling and innate immunity. Thus far, erythrophagocytosis has been studied by evaluating phagocytosis of erythrocytes that were damaged to mimic senescence. These studies have demonstrated that acquisition of some specific individual senescence markers can trigger erythrophagocytosis by macrophages, but we hypothesized that the mechanism of erythrophagocytosis of such damaged erythrocytes might differ from erythrophagocytosis of physiologically aged erythrocytes. Design and MethodsTo test this hypothesis we generated an erythrocyte population highly enriched in senescent erythrocytes by a hypertransfusion procedure in mice. Various erythrocyte-aging signals were analyzed and erythrophagocytosis was evaluated in vivo and in vitro. ResultsThe large cohort of senescent erythrocytes from hypertransfused mice carried numerous aging signals identical to those of senescent erythrocytes from control mice. Phagocytosis of fluorescently-labeled erythrocytes from hypertransfused mice injected into untreated mice was much higher than phagocytosis of labeled erythrocytes from control mice. However, neither erythrocytes from hypertransfused mice, nor those from control mice were phagocytosed in vitro by primary macrophage cultures, even though these cultures were able to phagocytose oxidatively damaged erythrocytes. ConclusionsThe large senescent erythrocyte population found in hypertransfused mice mimics physiologically aged erythrocytes. For effective erythrophagocytosis of these senescent erythrocytes, macrophages depend on some features of the intact phagocytosing tissue for support. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model

“…mice. 22,23 Gilson et al 24 as well as Hod et al 25 reported that after 14 days of storage in CPDA-1, murine RBCs had an in vivo 24-h RBC recovery of 64% to 65%, which is similar to the data from human RBCs stored for 42 days. 26 Yu et al reproduced the mature model, characterized the biochemical and functional effects, and studied the mechanisms responsible for the adverse effects of transfusing stored RBCs.…”

Red blood cells with elevated cytoplasmic Ca2+ are primarily taken up by splenic marginal zone macrophages and CD207+ dendritic cells

“…As such, exposure of phosphatidylserine (PS) may be a more important feature of eryptotic cells, compared with normally senescent RBCs. 3,12 Interestingly, an elevated [Ca 21 ] i has been found to be an important event in eryptosis induction in a majority of the cases, suggesting that this effector function could be one key mechanism behind eryptosis. 11,13 An increased [Ca 21 ] i is likely a consequence of Ca 21 entry through Ca 21 -permeable nonselective cation channels in the RBC membrane.…”

Changes in Erythrocyte Surface Marker Cd44 During Hypothermic and Low Temperature Storage

“…Зміни поверхневих мембранних маркерів при старінні, гіпотермічному зберіганні та розвитку патофізіологічних процесів в еритроцитах, корелюють зі зниженням життєздатності та стабільності клітин [1,2]. Вочевидь, поверхневі характеристики віддзеркалюють структурно-функціональні перебудови мембран, які викликані різними стресовими факторами.…”