A novel strategy for blocking chemokine mediated inflammation

Autor: Zoë Johnson, M. H. Kosco-Vilbois, A.E.I. Proudfoot, Timothy N. C. Wells, F. Borlat
Rok vydání: 2003
Předmět:
Zdroj: Scopus-Elsevier
ISSN: 1420-908X
1023-3830
Popis: Chemokines are chemoattractant proteins that are involved in basal trafficking, as well as recruitment and activation of cells in inflammatory processes. They are widely believed to act through a haptotactic mechanism, whereby immobilised gradients of chemokines are established on the endothelial cell surface and in the extracellular matrix [1]. Chemokines are known to bind to glycosaminoglycans (GAGs) in vitro and in vivo [2-4]. This GAG binding has been shown to promote oligomerisation [4], which has been hypothesised to increase local concentrations of chemokine in vivo [5]. Additionally, oligomerisation could enhance presentation to receptors [4, 6]. We recently demonstrated the essential role of the chemokine/GAG interaction with respect to biological activity in vivo [7], using a RANTES/CCL5 variant where the basic amino acids on the 40s loop were mutated to alanine, considerably reducing the capacity for heparin binding [8]. The aim ofthe present study was to investigate the potential of [44AANA47]-RANTES to block chemokine mediated inflammation in vivo.
Databáze: OpenAIRE
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