Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review.
Human red blood cells (RBCs) have a life-span of 120 days in circulation, after which they are phagocytized by resident macrophages. Extensive studies have been undertaken by many investigators in order to elucidate the cellular and molecular mechanisms of the erythrophagocytosis. The critical questions addressed by physiologists, clinicians and biochemists are: 'which of the many traumatic blemishes that appear on the erythrocyte surface as it winds its way through the circulation is the primary signal for clearance of the effete RBC from the circulation?', or 'What is the critical signal that it, and it alone, will activate the resident macrophage to adhere to and engulf it?'. Numerous, and often conflicting, hypotheses have been proposed. Each investigator focusing on but one of the many modifications that afflict the cell surface of the ageing erythrocyte, viz changes in either or both the carbohydrate or peptidic moieties of glycoproteins; abolishment of the pre-existing asymmetry in the lipid bilayer with the exposure of phosphatidylserine residues; or alterations in spectrin, to mention but a few. Many of these investigators also have invoked an intermediary role for auto-immune antibodies that recognise the change(s) on the erythrocyte surface and thereby serve as opsonins as a prelude to the erythrophagocytosis. The objective of the present review is to evaluate the data in support of the various hypotheses, and to submit some of our own recent observations involving the use of flow cytometric procedures that: i) provide evidence that the cell surface sialic acid serves as a determinant of the life-span; ii) characterise the senescent erythrocyte population that is specifically captured and phagocytized by macrophages (utilising the rapid and sensitive procedure we developed for quantification of in vitro erythrophagocytosis); and finally iii) provide evidence for the existence of an alternative pathway that is independent of immunoglobulins.
Bratosin
D
D
Institutut de Biochimie, Academia Romanà, Bucurest, Romania.
Mazurier
J
J
Tissier
J P
JP
Estaquier
J
J
Huart
J J
JJ
Ameisen
J C
JC
Aminoff
D
D
Montreuil
J
J
D000818:Animals; D002240:Carbohydrate Sequence; D002462:Cell Membrane / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000502:physiology*