Granulocyte-macrophage colony-stimulating factor and other cytokines regulate surface expression of the leukocyte adhesion molecule-1 on human neutrophils, monocytes, and their precursors.
Granulocyte-macrophage colony-stimulating factor and other cytokines regulate surface expression of the leukocyte adhesion molecule-1 on human neutrophils, monocytes, and their precursors.
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DOI：
10.4049/jimmunol.145.2.576
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发表时间：
1990-07
影响因子：
4.4
通讯作者：
James D. Griffin;O. Spertini;T. Ernst;M. Belvin;H. Levine;Y. Kanakura;T. Tedder
中科院分区：
文献类型：
--
作者：
James D. Griffin;O. Spertini;T. Ernst;M. Belvin;H. Levine;Y. Kanakura;T. Tedder
越来越多的证据表明，粒细胞-巨噬细胞 (GM)-CSF 等细胞因子可以在体外和体内深刻影响中性粒细胞的粘附、聚集和流动性。然而，这些因素可能改变中性粒细胞粘附特性的机制尚不完全清楚。最近通过 cDNA 克隆鉴定了一个新的细胞粘附分子家族。该家族的成员包括人白细胞粘附分子-1 (LAM-1)、人内皮白细胞粘附分子和高内皮小静脉的小鼠白细胞归巢受体 MEL-14。 LAM-1 是鼠 MEL-14 的人类同源物，被认为介导白细胞与人类高内皮微静脉的结合。 LAM-1 可以通过 mAb TQ-1、Leu 8 或抗 LAM1.1 进行识别。使用流式细胞术和抗 LAM-1.1 mAb 研究了 LAM-1 在粒细胞、单核细胞及其前体上的表达和调节。通过流式显微荧光测定，中性粒细胞、嗜酸性粒细胞、单核细胞、骨髓细胞、粒细胞/巨噬细胞集落形成单位和红系细胞爆发形成单位为LAM-1+。通过用细胞因子或其他刺激物处理各种细胞群0-90分钟来测试LAM-1表达的调节。中性粒细胞、单核细胞和骨髓细胞暴露于 GM-CSF 会导致细胞表面 LAM-1 快速完全丢失，但对淋巴细胞表达 LAM-1 没有影响。 LAM-1 的缺失在时间上与 CD11b (Mo1) 的上调相关，CD11b 是一种参与中性粒细胞聚集的粘附分子。已知可激活中性粒细胞的其他几种因素也会导致 LAM-1 下调和 CD11b 上调，包括 TNF、FMLP 和白三烯 B4。有趣的是，粒细胞-CSF 和 IFN-γ 对中性粒细胞 LAM-1 表达的影响很小。在单核细胞和骨髓前体细胞上观察到类似的结果。因此，中性粒细胞暴露于 GM-CSF 会导致粘附分子表面表达发生深刻变化，同时 CD11b 上调和 LAM-1 下调。粘附蛋白的这些变化可能会改变接受某些类型细胞因子治疗的患者成熟骨髓细胞及其前体细胞的聚集和活动性。
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.