Grayson M H, Van der Vieren M, Sterbinsky S A, Michael Gallatin W, Hoffman P A, Staunton D E, Bochner B S
The Johns Hopkins University School of Medicine, Division of Clinical Immunology, Baltimore, Maryland 21224, USA.
J Exp Med. 1998 Dec 7;188(11):2187-91. doi: 10.1084/jem.188.11.2187.
The beta2 family of integrins, CD11a, CD11b, CD11c, and alphad, are expressed on most leukocytes. We show that the newest member of this family, alphad, is expressed on human eosinophils in peripheral blood, and surface expression can be upregulated within minutes by phorbol ester or calcium ionophore A23187. Culture of eosinophils with interleukin 5 (IL-5) leads to a two- to fourfold increase in alphad levels by 3-7 d without a change in alpha4 integrin expression. Eosinophils isolated from late phase bronchoalveolar lavage fluids express alphad at levels similar to that seen after 3 d of IL-5 culture. Regarding alphadbeta2 ligands, in both freshly isolated and IL-5-cultured eosinophils, as well as alphadbeta2-transfected Chinese hamster ovary cells, alphadbeta2 can function as a ligand for vascular cell adhesion molecule 1 (VCAM-1). This conclusion is based on the ability of monoclonal antibodies to alphad, beta2, or VCAM-1 to block cell attachment in static adhesion assays. In experiments with eosinophils, the relative contribution of alphadbeta2 integrin- mediated adhesion is enhanced after IL-5 culture. These experiments demonstrate that alphadbeta2 is an alternative ligand for VCAM-1, and this integrin may play a role in eosinophil adhesion to VCAM-1 in states of chronic inflammation.
整合素β2家族的CD11a、CD11b、CD11c和αd在大多数白细胞上表达。我们发现该家族的最新成员αd在外周血中的人类嗜酸性粒细胞上表达，并且佛波酯或钙离子载体A23187可在数分钟内上调其表面表达。用白细胞介素5（IL-5）培养嗜酸性粒细胞3 - 7天可使αd水平增加2至4倍，而α4整合素的表达无变化。从晚期支气管肺泡灌洗液中分离出的嗜酸性粒细胞表达的αd水平与IL-5培养3天后的水平相似。关于αdβ2配体，在新鲜分离的和IL-5培养的嗜酸性粒细胞以及αdβ2转染的中国仓鼠卵巢细胞中，αdβ2均可作为血管细胞黏附分子1（VCAM-1）的配体。这一结论基于在静态黏附试验中，抗αd、β2或VCAM-1的单克隆抗体能够阻断细胞黏附的能力。在嗜酸性粒细胞实验中，IL-5培养后αdβ2整合素介导的黏附的相对贡献增强。这些实验表明αdβ2是VCAM-1的一种替代配体，并且这种整合素可能在慢性炎症状态下嗜酸性粒细胞与VCAM-1的黏附中发挥作用。
