Soluble E-selectin Acts in Synergy with Platelet-activating Factor to Activate Neutrophil β2-Integrins

• Published in: The Journal of biological chemistry 2000-05, Vol.275 (21), p.15758-15764
• Main Authors: Ruchaud-Sparagano, Marie-Hélène, Walker, Trevor R., Rossi, Adriano G., Haslett, Christopher, Dransfield, Ian
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M907390199

Selectins play a critical role in neutrophil recruitment to sites of inflammation, in tethering and rolling of neutrophils on vascular endothelium, as well as triggering β2-integrin-mediated adhesion. We have previously demonstrated potential pro-inflammatory effects of soluble E-selectin upon neutrophil effector functions, using a soluble recombinant molecule (E-zz), which increased β2-integrin-mediated adhesion, decreased β2-integrin-dependent migration, and triggered reactive oxygen species generation and release. In this study, we have examined the intracellular signals following neutrophil activation by soluble E-selectin. We show that exposure of neutrophils to E-selectin and platelet-activating factor (PAF) in combination induced a synergistic effect upon β2-integrin-mediated adhesion. Although soluble E-selectin did not induce Ca2+ mobilization in neutrophils by itself, elevation of intracellular Ca2+ was specifically prolonged in response to PAF but not leukotriene B4 orN-formyl-Met-Leu-Phe. The prolonged Ca2+mobilization observed in the presence of E-selectin was dependent on Ca2+ influx from intracellular stores rather than influx of extracellular Ca2+ through SKF 96365-sensitive channels. The specific alteration of Ca2+ mobilization reported here appears not to have a role in the synergistic effects of E-selectin and PAF upon neutrophil O⨪2 release but may be involved in augmentation of β2-integrin-mediated adhesion.