Griffin J D, Spertini O, Ernst T J, Belvin M P, Levine H B, Kanakura Y, Tedder T F
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1990 Jul 15;145(2):576-84.
There is increasing evidence that cytokines such as granulocyte-macrophage (GM)-CSF can profoundly affect the adhesion, aggregation, and mobility of neutrophils both in vitro and in vivo. However, the mechanisms whereby these factors might alter the adhesive properties of neutrophils are incompletely understood. A new family of cellular adhesion molecules has recently been identified by cDNA cloning. The members of this family include human leukocyte adhesion molecule-1 (LAM-1), the human endothelial-leukocyte adhesion molecule, and the mouse leukocyte homing receptor for high endothelial venules, MEL-14. LAM-1 is the human homologue of murine MEL-14, and is believed to mediate binding of leukocytes to human high endothelial venules. LAM-1 can be identified by mAb TQ-1, Leu 8, or anti-LAM1.1. The expression and regulation of LAM-1 on granulocytes, monocytes, and their precursors was investigated using flow cytometry and the anti-LAM-1.1 mAb. Neutrophils, eosinophils, monocytes, marrow myeloid cells, granulocyte/macrophage colony-forming unit, and burst-forming unit for erythroid cells were LAM-1+ by flow microfluorimetry. The regulation of LAM-1 expression was tested by treating various cell populations with cytokines or other stimuli for 0-90 min. Exposure of neutrophils, monocytes, and marrow myeloid cells to GM-CSF induced rapid and complete loss of LAM-1 from the cell surface, but had no effect on LAM-1 expression by lymphocytes. The loss of LAM-1 was temporally correlated with up-regulation of CD11b (Mo1), an adhesion molecule involved in neutrophil aggregation. Several other factors known to activate neutrophils also caused down-regulation of LAM-1 and up-regulation of CD11b, including TNF, FMLP, and leukotriene B4. Interestingly, granulocyte-CSF and IFN-gamma had minimal effects on neutrophil LAM-1 expression. Similar results were observed on monocytes and myeloid precursor cells. Thus, exposure of neutrophils to GM-CSF results in a profound change in surface expression of adhesion molecules, with coordinated up-regulation of CD11b and down-regulation of LAM-1. These changes in adhesion proteins are likely to alter aggregation and mobility of both mature myeloid cells and their precursors in patients receiving certain types of cytokine therapy.
越来越多的证据表明，诸如粒细胞巨噬细胞（GM）-集落刺激因子等细胞因子在体外和体内均可深刻影响中性粒细胞的黏附、聚集及移动。然而，这些因子改变中性粒细胞黏附特性的机制尚未完全明了。最近通过cDNA克隆鉴定出了一个新的细胞黏附分子家族。该家族成员包括人白细胞黏附分子-1（LAM-1）、人内皮细胞-白细胞黏附分子以及小鼠高内皮微静脉白细胞归巢受体MEL-14。LAM-1是鼠MEL-14的人类同源物，被认为介导白细胞与人高内皮微静脉的结合。LAM-1可通过单克隆抗体TQ-1、Leu 8或抗LAM1.1识别。使用流式细胞术和抗LAM-1.1单克隆抗体研究了LAM-1在粒细胞、单核细胞及其前体细胞上的表达及调控。通过流式微量荧光测定法可知，中性粒细胞、嗜酸性粒细胞、单核细胞、骨髓髓细胞、粒细胞/巨噬细胞集落形成单位以及红细胞爆式集落形成单位均为LAM-1阳性。通过用细胞因子或其他刺激物处理各种细胞群体0至90分钟来测试LAM-1表达的调控。中性粒细胞、单核细胞和骨髓髓细胞暴露于GM-CSF会导致细胞表面LAM-1迅速且完全丧失，但对淋巴细胞的LAM-1表达无影响。LAM-1的丧失在时间上与参与中性粒细胞聚集的黏附分子CD11b（Mo1）的上调相关。已知的其他几种激活中性粒细胞的因子也会导致LAM-1下调和CD11b上调，包括肿瘤坏死因子、甲酰甲硫氨酸-亮氨酸-苯丙氨酸以及白三烯B4。有趣的是，粒细胞集落刺激因子和γ干扰素对中性粒细胞LAM-1表达的影响极小。在单核细胞和髓前体细胞上也观察到了类似结果。因此，中性粒细胞暴露于GM-CSF会导致黏附分子表面表达发生深刻变化，同时CD11b上调且LAM-1下调。在接受某些类型细胞因子治疗的患者中，这些黏附蛋白的变化可能会改变成熟髓细胞及其前体细胞的聚集和移动。
