Chuang P I, Yee E, Karsan A, Winn R K, Harlan J M
Department of Medicine, University of Washington, Seattle, Washington, USA.
Biochem Biophys Res Commun. 1998 Aug 19;249(2):361-5. doi: 10.1006/bbrc.1998.9155.
During the process of terminal differentiation toward mature neutrophils, the anti-apoptotic proteins Bcl-2 and Bcl-x become down-regulated and eventually cease to be expressed, whereas the death-promoting Bcl-2 homologue, Bax, persists. Thus, the disappearance of anti-apoptotic homologues was thought to account for the early demise of mature neutrophils. However, although the survival of mature human neutrophils can be prolonged by a variety of factors, no anti-apoptotic Bcl-2 homologues have previously been identified. Human A1 is a Bcl-2 homologue previously shown to be present in endothelial cells and to convey anti-apoptotic function in vitro. We describe here that human A1 mRNA is constitutively expressed in mature neutrophils and is up-regulated by G-CSF and LPS, agonists that promote neutrophil survival. In addition, we show progressive A1 mRNA accumulation in HL-60 cells during all-trans retinoic acid-driven neutrophilic differentiation. Our findings suggest that A1 may have an important role in neutrophilic development and in modulating mature neutrophil survival.
在向成熟中性粒细胞终末分化的过程中，抗凋亡蛋白Bcl-2和Bcl-x表达下调并最终停止表达，而促凋亡的Bcl-2同源物Bax持续存在。因此，抗凋亡同源物的消失被认为是成熟中性粒细胞早期死亡的原因。然而，尽管多种因素可延长成熟人中性粒细胞的存活时间，但此前尚未鉴定出抗凋亡的Bcl-2同源物。人A1是一种Bcl-2同源物，先前已证明其存在于内皮细胞中，并在体外具有抗凋亡功能。我们在此描述，人A1 mRNA在成熟中性粒细胞中组成性表达，并被促进中性粒细胞存活的激动剂G-CSF和LPS上调。此外，我们显示在全反式维甲酸驱动的HL-60细胞嗜中性分化过程中，A1 mRNA逐渐积累。我们的研究结果表明，A1可能在嗜中性粒细胞发育和调节成熟中性粒细胞存活中起重要作用。
