Geiser T, Dewald B, Ehrengruber M U, Clark-Lewis I, Baggiolini M
Theodor-Kocher Institute, University of Bern, Switzerland.
J Biol Chem. 1993 Jul 25;268(21):15419-24.
GRO alpha, a protein structurally related to interleukin-8 (IL-8) and originally described as a melanoma growth stimulatory factor, possesses potent neutrophil-stimulating activity. Recently, two closely related genes, gro beta and gro gamma, were identified. In the present work, the three GRO proteins were chemically synthesized, and their biological activities on human neutrophils and other leukocytes were compared. GRO alpha, GRO beta, and GRO gamma, like IL-8, induced chemotaxis, shape change, a rise in intracellular free calcium levels, exocytosis, and the respiratory burst in neutrophils. The GRO proteins were also active toward basophils as shown by chemotaxis and intracellular calcium concentration changes. The order of potency in neutrophils and basophils was IL-8 > GRO alpha > or = GRO gamma > GRO beta. Of the two IL-8 receptors expressed on human neutrophils, one binds GRO alpha with high and the other with low affinity. Competition binding experiments using radiolabeled IL-8 and GRO alpha revealed the same characteristics for GRO beta and GRO gamma. Similarly, cross-desensitization, as assessed by the stimulus-dependent changes in intracellular calcium concentration, indicated that all three GRO proteins interact with common receptors. From these results, it can be concluded that GRO alpha, GRO beta, and GRO gamma have the same pattern of activity toward human granulocytes and that the differences in amino acid sequence among these proteins have only minor effects on biological activity.
GROα是一种在结构上与白细胞介素-8（IL-8）相关的蛋白质，最初被描述为黑色素瘤生长刺激因子，具有强大的刺激中性粒细胞的活性。最近，人们鉴定出了两个密切相关的基因，即groβ和groγ。在本研究中，我们化学合成了这三种GRO蛋白，并比较了它们对人中性粒细胞和其他白细胞的生物学活性。GROα、GROβ和GROγ与IL-8一样，可诱导中性粒细胞的趋化性、形态变化、细胞内游离钙水平升高、胞吐作用和呼吸爆发。趋化性和细胞内钙浓度变化表明，GRO蛋白对嗜碱性粒细胞也有活性。在中性粒细胞和嗜碱性粒细胞中，活性顺序为IL-8>GROα≥GROγ>GROβ。在人中性粒细胞上表达的两种IL-8受体中，一种与GROα高亲和力结合，另一种与GROα低亲和力结合。使用放射性标记的IL-8和GROα进行的竞争结合实验显示，GROβ和GROγ具有相同的特性。同样，通过细胞内钙浓度的刺激依赖性变化评估的交叉脱敏表明，所有三种GRO蛋白都与共同受体相互作用。从这些结果可以得出结论，GROα、GROβ和GROγ对人粒细胞具有相同的活性模式，并且这些蛋白质之间氨基酸序列的差异对生物学活性只有微小影响。
