The influence of glycosaminoglycans on IL-8-mediated functions of neutrophils

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• 作者：Denise Schlorke^a ; ^c ; Lars Thomas^a ; Sergey A. Samsonov^b ; Daniel Huster^a ; Jü ; rgen Arnhold^a ; ^c ; Annelie Pichert^a ; ^{Annelie.Pichert@medizin.uni-leipzig.de}
• 关键词：Glycosaminoglycans ; Interleukin-8 ; Neutrophils ; Chemotaxis ; Oxidative activity
• 刊名：Carbohydrate Research
• 出版年：2012
• 出版时间：15 July, 2012
• 年：2012
• 卷：356
• 期：Complete
• 页码：196-203
• 全文大小：731 K

文摘

Glycosaminoglycans (GAGs) of the extracellular matrix (ECM) contribute to the regulation of physiological processes by binding various immune-competent proteins. Due to their large structural diversity, the analysis of the binding properties and their functional consequences is challenging. The cytokine interleukin-8 (IL-8) is involved in the recruitment of neutrophils to inflammatory sites. Here, we investigated the interaction of heparin hexasaccharides and recombinant human IL-8, consisting of 77 amino acids using fluorescence and NMR spectroscopy. A dissociation constant of 2.0 ¡À 0.4 ¦ÌM was determined for the heparin-IL-8 complex, which is slightly higher than what has been found for chondroitin-6-sulfate (K_D = 1.4 ¡À 0.4 ¦ÌM) [Pichert, A.; Samsonov, S. A.; Theisgen, S.; Thomas, L.; Baumann, L.; Schiller, J.; Beck-Sickinger, A. G.; Huster, D.; Pisabarro, M. T. Glycobiology 2012, 22, 134-145], suggesting an important role of the sulfate group at position 6 of the second ring in the disaccharide unit of the GAGs in this interaction. In addition, the influence of long-chain hyaluronan, chondroitin sulfate, and heparin on IL-8-induced chemotaxis and oxidative activity of neutrophils was examined. Only the incubation of heparin with IL-8 affected the IL-8-mediated chemotaxis of neutrophils. However, all investigated GAGs enhanced the IL-8-induced formation of reactive oxygen species in neutrophils, which is an entirely new finding. This work provides a representative example of how protein functions can be regulated by different GAGs of the ECM.