Format:
Online-Ressource
ISSN:
1521-4141
Content:
Abstract: Interleukin‐8 (IL‐γ) acts on human neutrophils via two receptors, CXCR1 and CXCR2. It shares CXCR2 with all neutrophil‐activating chemokines, which like IL‐8 have a conserved Glu‐Leu‐Arg (ELR) N‐terminal motif, but is generally considered to be the only relevant agonist for CXCR1. IL‐8 has a basic residue at the sixth position after the second cysteine, which was suggested to contribute to CXCR1 specificity. Among the other ELR chemokines, only granulocyte chemotactic protein 2 (GCP‐2) has such a basic determinant. Using Jurkat cells that stably express either CXCR1 or CXCR2, we studied receptor activation by IL‐8, GCP‐2 epithelial neutrophil‐activating protein 2 (ENA‐78) (which shares 77 % identical amino acids with GCP‐2) and growth‐regulated oncogene α (GROα). At 10 nM and higher concentrations, GCP‐2 and IL‐8 induced significant activation of CXCR1‐expressing cells, but no activity was found with GROα and ENA‐78. As expected, however, all four chemokines had similar activities on CXCR2‐expressing cells. A variant of GCP‐2 in which the basic residue, Arg20, was replaced by a glycine was synthesized. This derivative was ineffective on CXCR1, but was as active as wild‐type GCP‐2 in CXCR2‐expressing cells. GCP‐2 displaced radiolabeled IL‐8 from both receptors with low affinity, and in this respect resembled ENA‐78 and GROα. Our data show that GCP‐2 acts via both IL‐8 receptors and thus appears to be functionally more similar to IL‐8 than to the other ELR chemokines. Activation of CXCR1 appears to depend significantly on the presence of a basic binding determinant close to the second cysteine.
In:
volume:28
In:
number:1
In:
year:2006
In:
pages:164-170
In:
extent:7
In:
European journal of immunology, Weinheim : Wiley-VCH, 1971-, 28, Heft 1 (2006), 164-170 (gesamt 7), 1521-4141
Language:
English
DOI:
10.1002/(SICI)1521-4141(199801)28:01〈164::AID-IMMU164〉3.0.CO;2-S
URN:
urn:nbn:de:101:1-2023112606014097079044
URL:
https://doi.org/10.1002/(SICI)1521-4141(199801)28:01〈164::AID-IMMU164〉3.0.CO;2-S
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023112606014097079044
URL:
https://d-nb.info/1311195505/34
URL:
https://doi.org/10.1002/(SICI)1521-4141(199801)28:01〈164::AID-IMMU164〉3.0.CO;2-S