[HTML][HTML] Characterization of two high affinity human interleukin-8 receptors.

J Lee, R Horuk, GC Rice, GL Bennett… - Journal of Biological …, 1992 - Elsevier
J Lee, R Horuk, GC Rice, GL Bennett, T Camerato, WI Wood
Journal of Biological Chemistry, 1992Elsevier
Interleukin 8 (IL-8) and melanocyte growth-stimulatory activity/gro (MGSA) are structurally
related proinflammatory cytokines that are chemoattractants and activators of neutrophils.
Recently, cDNA clones encoding a high affinity IL-8 receptor (IL-8R-A) and a “low affinity” IL-
8 receptor (IL-8R-B) have been isolated from human cDNA libraries. These two receptors
have 77% amino acid identity and are members of the G protein-coupled superfamily of
receptors with seven transmembrane domains. We have expressed these two receptors in …
Interleukin 8 (IL-8) and melanocyte growth-stimulatory activity/gro (MGSA) are structurally related proinflammatory cytokines that are chemoattractants and activators of neutrophils. Recently, cDNA clones encoding a high affinity IL-8 receptor (IL-8R-A) and a “low affinity” IL-8 receptor (IL-8R-B) have been isolated from human cDNA libraries. These two receptors have 77% amino acid identity and are members of the G protein-coupled superfamily of receptors with seven transmembrane domains. We have expressed these two receptors in mammalian cells and find that in this system both receptors bind IL-8 with high affinity (Kd approximately 2 nM). The receptor affinities differ for MGSA, however. IL-8R-A binds MGSA with low affinity (Kd approximately 450 nM); IL-8R-B binds MGSA with high affinity (Kd approximately 2 nM). The transfected cells respond to ligand binding with a transient increase in the intracellular Ca2+ concentration. A Ca2+ response is found for IL-8R-A following the binding of IL-8; no response is found for MGSA. A Ca2+ response for IL-8R-B follows the binding of both ligands. Blot hybridization with oligonucleotide probes specific for the two receptors shows that mRNA for both receptors is present in human neutrophils. Analysis of IL-8 and MGSA binding data on neutrophils as well as Ca2+ response and desensitization data shows that the presence of these two IL-8 receptors on the cell surface can account for the profile of these two ligands on neutrophils.
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