Molecular requirements for sorting of the chemokine interleukin-8/CXCL8 to endothelial Weibel-Palade bodies

J Biol Chem. 2009 Aug 28;284(35):23532-9. doi: 10.1074/jbc.M900874200. Epub 2009 Jul 3.


Sorting of proteins to Weibel-Palade bodies (WPB) of endothelial cells allows rapid regulated secretion of leukocyte-recruiting P-selectin and chemokines as well as procoagulant von Willebrand factor (VWF). Here we show by domain swap studies that the exposed aspartic acid in loop 2 (Ser(44)-Asp(45)-Gly(46)) of the CXC chemokine interleukin (IL)-8 is crucial for targeting to WPB. Loop 2 also governs sorting of chemokines to alpha-granules of platelets, but the fingerprint of the loop 2 of these chemokines differs from that of IL-8. On the other hand, loop 2 of IL-8 closely resembles a surface-exposed sequence of the VWF propeptide, the region of VWF that directs sorting of the protein to WPB. We conclude that loop 2 of IL-8 constitutes a critical signal for sorting to WPB and propose a general role for this loop in the sorting of chemokines to compartments of regulated secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cells, Cultured
  • Endothelial Cells / chemistry
  • Endothelial Cells / metabolism*
  • Female
  • Humans
  • Interleukin-8 / chemistry*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Protein Transport
  • Sequence Alignment
  • Weibel-Palade Bodies / chemistry
  • Weibel-Palade Bodies / genetics
  • Weibel-Palade Bodies / metabolism*


  • Interleukin-8