Loetscher P, Seitz M, Clark-Lewis I, Baggiolini M, Moser B
Theodor-Kocher Institute, University of Bern, Switzerland.
FEBS Lett. 1994 Mar 21;341(2-3):187-92. doi: 10.1016/0014-5793(94)80454-0.
Neutrophil leukocytes, the target cells for interleukin-8 and related CXC chemokines, bear high numbers of two types of IL-8 receptors (IL-8R1 and IL-8R2). By cDNA transfection Jurkat cell lines were generated that stably express either IL-8R1 or IL-8R2 (J-IL8R1 and J-IL8R2). J-IL8R1 expressed 4,000 +/- 1,000 copies of IL-8R1, and bound IL-8 with high affinity (Kd 1-4 nM) and GRO alpha and NAP-2 with low affinity (Kd 200-500 nM). J-IL8R2 expressed 17,000 +/- 3,000 copies of IL-8R2, and bound all three chemokines with high affinity. Both transfectants showed a similar degree of chemotactic migration after stimulation with IL-8, GRO alpha and NAP-2. All three chemokines were equally potent as attractants of J-IL8R2, whereas IL-8 was 300 to 1,000-fold more potent than GRO alpha or NAP-2 as attractant of J-IL8R1. The potencies, therefore, agree with the affinities of the ligands to IL-8R1 and IL-8R2. Our results demonstrate that both IL-8 receptors function independently, and mediate chemotaxis in response to IL-8 and other CXC chemokines.
中性粒细胞是白细胞介素-8及相关CXC趋化因子的靶细胞,其上有大量两种类型的白细胞介素-8受体(IL-8R1和IL-8R2)。通过cDNA转染生成了稳定表达IL-8R1或IL-8R2的Jurkat细胞系(J-IL8R1和J-IL8R2)。J-IL8R1表达4000±1000个IL-8R1拷贝,与IL-8高亲和力结合(解离常数1 - 4 nM),与GROα和NAP-2低亲和力结合(解离常数200 - 500 nM)。J-IL8R2表达17000±3000个IL-8R2拷贝,与所有三种趋化因子都高亲和力结合。在用IL-8、GROα和NAP-2刺激后,两种转染细胞系均表现出相似程度的趋化迁移。所有三种趋化因子作为J-IL8R2的吸引剂效力相当,而IL-8作为J-IL8R1的吸引剂比GROα或NAP-2效力高300至1000倍。因此,效力与配体对IL-8R1和IL-8R2的亲和力一致。我们的结果表明,两种白细胞介素-8受体独立发挥作用,并介导对IL-8和其他CXC趋化因子的趋化作用。