IL-8 AND NAP-2 DIFFER IN THEIR CAPACITIES TO BIND AND CHEMOATTRACT 293 CELLS TRANSFECTED WITH EITHER IL-8 RECEPTOR TYPE A OR TYPE B

Two receptors for interleukin 8 (IL-8) IL-8rA and IL-8rB, have been cloned. Previous studies of neutrophils indicated that the two C-X-C chemokines, IL-8 and NAP-2, bind to IL-8rB with high affinity but that only IL-8 binds to IL-8rA with high affinity. In this study, human kidney embryonal 293 cell...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 1997, Vol.9 (1), p.37-45
Main Authors: Ben-Baruch, Adit, Bengali, Kathleen, Tani, Kenji, Xu, Luoling, Oppenheim, Joost J., Wang, Ji Ming
Format: Article
Language:English
Subjects:
Antigens, CD - metabolism
beta-Thromboglobulin
Binding, Competitive
Cell Line
Chemotaxis - physiology
Humans
IL-8
IL-8 receptors
Interleukin-8 - metabolism
NAP-2
Peptides - metabolism
Protein Binding
Receptors, Interleukin - metabolism
Receptors, Interleukin-8A
Signal Transduction - physiology
Transfection
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Summary:Two receptors for interleukin 8 (IL-8) IL-8rA and IL-8rB, have been cloned. Previous studies of neutrophils indicated that the two C-X-C chemokines, IL-8 and NAP-2, bind to IL-8rB with high affinity but that only IL-8 binds to IL-8rA with high affinity. In this study, human kidney embryonal 293 cells were transfected to express solely IL-8rA or IL-8rB (the cells are designated IL-8rA/293 and IL-8rB/293, respectively). The authors show that NAP-2 bound both IL-8rA and IL-9rB specifically. While NAP-2 and IL-8 bound IL-8rB with comparable high affinity (2.9 ± 0.5) and 2.8 ± 0.8 nM, respectively), NAP-2 showed a lower binding affinity to IL-8rA (9 ± 2 nM) compared with IL-8 (1.3 ± 0.5 nM). A lower number of binding sites was detected for NAP-2 than for IL-8 on IL-8rA/293 cells as well on IL-8rB/293 cells. On both cell types (IL-8rA/293 and IL-8rB/293), NAP-2 and IL-8 could completely inhibit [ 125I]NAP-2 binding, while unlabelled NAP-2 could only partially compete for [ 125I]IL-8 binding. Functional assays revealed that although NAP-2 is chemotactic for both IL-8rA/293 and IL-8rB/293 cells, it is less potent than IL-8. While NAP-2 induced chemotaxis of IL-8rB/293 cells at the same optimal concentrations as IL-8 (10–100 ng/ml), the induction of optimal migratory response of IL-8rA/293 cells required much higher concentrations of NAP-2 than IL-8 (1000–3000 ng/ml and 10–100 ng/ml, respectively). The dose–response curve of the IL-8rB/293 cells to IL-8 was bell shaped, while the response to NAP-2 was sustained at a plateau level even at concentrations as high as 3000 ng/ml. It is likely that tertiary structural differences between NAP-2 and IL-8 account for their divergent abilities to bind and chemoattract 293 cells transfected with either IL-8 receptor type A or type B.
ISSN:1043-4666
1096-0023
DOI:10.1006/cyto.1996.0133