BOTH INTERLEUKIN-8 RECEPTORS INDEPENDENTLY MEDIATE CHEMOTAXIS - JURKAT CELLS TRANSFECTED WITH IL-8R1 OR IL-8R2 MIGRATE IN RESPONSE TO IL-8, GRO-ALPHA AND NAP-2

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 (K(d) 1-4 nM) and GROalpha and NAP-2 with low affinity (K(d) 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, GROalpha 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 GROalpha 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.