RANTES (CCL5) induces a CCR5-dependent accelerated shedding of syndecan-1 (CD138) and syndecan-4 from HeLa cells and forms complexes with the shed ectodomains of these proteoglycans as well as with those of CD44

Glycobiology. 2005 Feb;15(2):119-30. doi: 10.1093/glycob/cwh148. Epub 2004 Sep 8.


We recently demonstrated that RANTES forms complexes with CCR5, syndecan-1 (SD-1), SD-4, and CD44 expressed by human primary macrophages and that SD-1 and SD-4 but neither CD44 nor SD-2 coimmunoprecipitate with CCR5. Here we show that RANTES directly binds in a glycosaminoglycan-dependent manner to SD-1, SD-4, and CD44. Moreover, RANTES accelerates the shedding of SD-1 and SD-4 ectodomains from HeLa cells expressing CCR5 and, by contrast, has no effect on the constitutive shedding of CD44 from these cells. These accelerated sheddings are prevented by the MEK1/2 inhibitor, U0126, and by the protein kinase C inhibitor bisindolylmaleimide I. This indicates that both MAP kinase--and protein kinase C-dependent signaling pathways are involved in these RANTES-induced accelerated sheddings. RANTES also induces a decreased expression of SD-1 and SD-4 by HeLa cells expressing CCR5 and on the contrary an increased expression of CD44 by these cells. By contrast, RANTES neither accelerates the shedding of SD-1 and SD-4 ectodomains from HeLa cells lacking CCR5, nor changes the SD-1-, SD-4-, and CD44-plasma membrane expressions of these cells. CCR5 is therefore involved in the RANTES-induced accelerated shedding of SD-1 and SD-4 ectodomains. Nevertheless, the fact that RANTES stimulates in Hela cells (expressing or lacking CCR5) the mRNA synthesis of SD-1 and SD-4 indicates that the molecular events that follow the synthesis of these proteoglycans differ, according to the presence or not of CCR5. Finally, RANTES forms GAG-dependent complexes with the shed ectodomains of SD-1 and SD-4 as well as with those of CD44. The role of these events in the pathophysiology of RANTES deserves further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CCL5 / pharmacology*
  • Chemokine CCL5 / physiology
  • Gene Expression / genetics
  • HeLa Cells
  • Humans
  • Hyaluronan Receptors / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology
  • Membrane Glycoproteins / metabolism*
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Proteoglycans / metabolism*
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Syndecan-1
  • Syndecan-4
  • Syndecans
  • Transfection


  • Chemokine CCL5
  • Hyaluronan Receptors
  • Membrane Glycoproteins
  • Proteoglycans
  • Receptors, CCR5
  • SDC1 protein, human
  • SDC4 protein, human
  • Syndecan-1
  • Syndecan-4
  • Syndecans