IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways

These results indicate that IL-8 activates both the CXCR1 and the CXCR2 on microvascular endothelial cells, using different signal transduction cascades

Ingrid U. Schraufstatter; Janice Chung; Meike Burger


Scholarcy highlights

  • INTERLEUKIN-8 is a member of the C-X-C family of chemokines that shows high-affinity binding to the CXCR1 and the CXCR2
  • The CXCR1 is selectively activated by IL-8 only, the CXCR2 responds to several additional chemokines including growth-related protein-␣, neutrophil-activating peptide-2, and epithelial-derived neutrophil attractant-78
  • Pertussis toxin blocks all aspects of IL-8-mediated leukocyte activation, indicating that both the CXCR1 and CXCR2 are coupled to Gi in neutrophils where G␣i-2 is very abundant
  • Dominant negative Rac still translocates to the plasma membrane but fails to produce the downstream retractive cytoskeletal response. It has been known for several years that IL-8 and other ELR-containing C-X-C chemokines are angiogenic factors in vivo, the mechanism involved has remained unresolved because the presence of IL-8 receptors on cultured endothelial cells has been disputed
  • We report that microvascular endothelial cells responded to IL-8 on all occasions in vitro and that this response resulted from combined activation of the CXCR1 and the CXCR2
  • These functional studies are in agreement with the recent findings of Murdoch et al, who detected the CXCR1 and the CXCR2 on endothelial cells by RT-PCR and fluorescence-activated cell-sorter analysis with specific anti-receptor antibodies
  • The later effect of IL-8 or the effect of GRO␣, which stimulates the CXCR2 only, was blocked by pertussis toxin, indicating that the CXCR2 in endothelial cells couples to Gi. In contrast to the transient response in leukocytes, which lasts for less than 5 min, activation of the CXCR2 on endothelial cells lasted for more than 1 h

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