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© Charles Dauguet
Virus VIH-1 (HIV-1), agent du sida, à la surface d'un lymphocyte. Image colorisée.
Publication : Immunogenetics

A natural CCL5/RANTES variant antagonist for CCR1 and CCR3

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Immunogenetics - 22 Jun 2006

Capoulade-Métay C, Ayouba A, Kfutwah A, Lole K, Pêtres S, Dudoit Y, Deterre P, Menu E, Barré-Sinoussi F, Debré P, Theodorou I

Link to Pubmed [PMID] – 16791620

Immunogenetics 2006 Jul;58(7):533-41

The N-terminal domain of the chemokine CCL5/regulated upon activation normal T cell expressed and secreted (RANTES) has been shown to be critical for its biological activity on leukocytes. Several N-terminus-modified CCL5/RANTES derivatives, such as N-Terminal truncated CCL5/RANTES, Met-RANTES, and amino-oxypentane (AOP)-RANTES exhibited antagonist or partial agonist functions when investigated on the properties of their receptors CCR1, CCR3, and CCR5. Studying 95 African samples from Cameroon, we found a naturally occurring variant of CCL5/RANTES containing a missense mutation located in the first amino acid of the secreted form (S24F). S24F binds CCR1, CCR3, and CCR5 and triggers receptor down-modulation comparable to CCL5/RANTES. Moreover, in CCR5 positive cells, S24F elicits cellular calcium mobilization equivalent to that obtained with CCL5/RANTES. By contrast, S24F does not provoke any response in CCR1 and CCR3 positive cells. As CCL5/RANTES is able to attract different subtypes of leukocytes into inflamed tissue and intervenes in a wide range of allergic and autoimmune diseases, the discovery of this natural N-terminus-modified CCL5/RANTES analogue exhibiting differential effects on CCL5/RANTES receptors, opens up additional perspectives for therapeutic intervention.

http://www.ncbi.nlm.nih.gov/pubmed/16791620