Differential usage of the CXC chemokine receptors 1 and 2 by interleukin-8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78

Eur J Biochem. 1998 Jul 1;255(1):67-73. doi: 10.1046/j.1432-1327.1998.2550067.x.


The inflammatory response is mediated by a family of chemotactic cytokines, designated chemokines. The receptor usage of the CXC chemokine granulocyte chemotactic protein-2 (GCP-2) was compared with that of interleukin-8 (IL-8) and epithelial-cell-derived neutrophil attractant-78 (ENA-78). Chemokine activities were evaluated by measurement of intracellular calcium increase and by chemotaxis and binding assays, using CXC chemokine receptor (CXCR)-transfected cell lines. GCP-2 was equally potent at inducing a rise in [Ca2+]i in both CXCR1-transfected and CXCR2-transfected cells (minimal effective concentration 3 nM). IL-8 augmented the [Ca2+]i more efficiently in CXCR1-transfectants than in CXCR2-transfectants, whereas for ENA-78, threefold higher concentrations were necessary to obtain a calcium response in CXCR1-transfected cells than in CXCR2-transfectants. GCP-2 desensitized the calcium increase induced by IL-8 in both CXCR1-transfected and CXCR2-transfected cells, but ENA-78 only affected the IL-8-induced calcium response in CXCR2-transfectants. The half-maximal effective concentrations for migration of CXCR2-transfectants in response to GCP-2 and ENA-78 were similar (0.1 nM), whereas GCP-2 was tenfold more potent than ENA-78 on CXCR1-transfectants. Half-maximal migration of CXCR1-transfected and CXCR2-transfected cells was obtained with IL-8 at concentrations of no more than 0.01 nM. Radiolabeled IL-8 could efficiently be displaced from CXCR2 by IL-8, GCP-2 and ENA-78. In contrast, only IL-8 and GCP-2 but not ENA-78, competed for 125I-IL-8 binding to CXCR1. From these data, it can be concluded that, in addition to IL-8, GCP-2, but not ENA-78, efficiently binds to both CXCR1 and CXCR2. The differential receptor usage of the structurally related ELR+ CXC chemokines GCP-2 and ENA-78 is indicative of a different role in inflammatory reactions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Calcium / metabolism
  • Cells, Cultured
  • Chemokine CXCL5
  • Chemokine CXCL6
  • Chemokines, CXC / metabolism*
  • Chemotaxis, Leukocyte
  • Epithelial Cells / cytology
  • Humans
  • Interleukin-8 / analogs & derivatives*
  • Interleukin-8 / metabolism*
  • Kidney / cytology
  • Kidney / embryology
  • Ligands
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Transfection


  • Antigens, CD
  • CXCL5 protein, human
  • CXCL6 protein, human
  • Chemokine CXCL5
  • Chemokine CXCL6
  • Chemokines, CXC
  • Interleukin-8
  • Ligands
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Recombinant Proteins
  • Calcium