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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.
Charnaux, Nathalie; Brule, Séverine; Chaigneau, Thomas; Saffar, Line; Sutton, Angela; Hamon, Morgan; Prost, Catherine; Lievre, Nicole; Vita, Claudio; Gattegno, Liliane.
Afiliação
  • Charnaux N; Laboratoire de Biologie Cellulaire, Biothérapies Bénéfices et Risques, UPRES 3410 Université Paris XIII, 74, rue Marcel Cachin, 93017, Bobigny, France.
Glycobiology ; 15(2): 119-30, 2005 Feb.
Article em En | MEDLINE | ID: mdl-15355933
ABSTRACT
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.
Assuntos
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Base de dados: MEDLINE Assunto principal: Proteoglicanas / Glicoproteínas de Membrana / Quimiocina CCL5 / Receptores de Hialuronatos / Receptores CCR5 Limite: Humans Idioma: En Ano de publicação: 2005 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Proteoglicanas / Glicoproteínas de Membrana / Quimiocina CCL5 / Receptores de Hialuronatos / Receptores CCR5 Limite: Humans Idioma: En Ano de publicação: 2005 Tipo de documento: Article