Bratosin D, Mazurier J, Tissier J P, Estaquier J, Huart J J, Ameisen J C, Aminoff D, Montreuil J
Institutut de Biochimie, Academia Romanà, Bucurest, Romania.
Biochimie. 1998 Feb;80(2):173-95. doi: 10.1016/s0300-9084(98)80024-2.
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.
人类红细胞(RBCs)在循环中的寿命为120天,之后它们会被驻留的巨噬细胞吞噬。许多研究者进行了广泛的研究,以阐明红细胞吞噬作用的细胞和分子机制。生理学家、临床医生和生物化学家所关注的关键问题是:“在红细胞在循环中运行时出现在其表面的众多创伤性瑕疵中,哪一个是将衰老红细胞从循环中清除的主要信号?” 或者 “什么是唯一能激活驻留巨噬细胞附着并吞噬它的关键信号?”。已经提出了许多且常常相互矛盾的假说。每位研究者仅关注衰老红细胞细胞表面众多修饰中的一种,即糖蛋白的碳水化合物或肽部分的变化,或两者皆有;脂质双层中预先存在的不对称性被消除,磷脂酰丝氨酸残基暴露;或血影蛋白的改变等等。许多这些研究者还援引了自身免疫抗体的中介作用,这些抗体识别红细胞表面的变化,从而作为调理素,为红细胞吞噬作用做铺垫。本综述的目的是评估支持各种假说的数据,并提交我们自己最近的一些观察结果,这些观察涉及使用流式细胞术程序:i)提供证据表明细胞表面唾液酸是寿命的决定因素;ii)表征被巨噬细胞特异性捕获和吞噬的衰老红细胞群体(利用我们开发用于体外红细胞吞噬作用定量的快速且灵敏的程序);最后iii)提供存在一条独立于免疫球蛋白的替代途径的证据。