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

Publisher: Ferrata Storti Foundation Country of Publication: Italy NLM ID: 0417435 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1592-8721 (Electronic) Linking ISSN: 03906078 NLM ISO Abbreviation: Haematologica Subsets: MEDLINE

Publication: 1999- : Pavia, Italy : Ferrata Storti Foundation
Original Publication: Pavia [etc.]

Erythrocyte Aging/*physiology ; Erythrocytes/*physiology ; Macrophages/*physiology ; Phagocytosis/*physiology; Animals ; Biomarkers/analysis ; Biotinylation ; Erythrocyte Transfusion ; Erythrocytes/cytology ; Erythropoiesis/physiology ; Female ; Flow Cytometry ; Humans ; Iron/metabolism ; Macrophages/cytology ; Male ; Mice ; Mice, Inbred C57BL ; Oxidation-Reduction ; Primary Cell Culture ; Reactive Oxygen Species/metabolism

Background: The 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 Methods: To 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.
Results: The 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.
Conclusions: The 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.

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0 (Biomarkers)
0 (Reactive Oxygen Species)
E1UOL152H7 (Iron)

Date Created: 20120215 Date Completed: 20121231 Latest Revision: 20211021

20250114

PMC3396668

10.3324/haematol.2011.057620

22331264