Pneumologie 2011; 65 - P231
DOI: 10.1055/s-0031-1272049

The effect of endothelin-1 on human basophil function in vitro

K Cima 1, S Blunder 1, S Desole 1, J Günther 1, C Kähler 1
  • 1Pneumologie, Innere Medizin I, Department für Innere Medizin, Medizinische Universität Innsbruck

Endothelin-1 (ET-1) has proinflammatory properties and contributes to allergic late-phase responses. As basophils play a key role in allergic rhinitis or asthma, we investigated the effect of ET-1 on basophils.

Cells were isolated from venous blood of healthy donors via magnetic cell sorting (MACS®). Basophils migrated towards ET-1 [10–6-10–16 M] or MCP-1 [10–8 M] (positive control) for 90min in modified Boyden chambers. To explore whether ETA or ETB receptors are involved, cells were preincubated with BQ-123 [10–6-10–16 M] or BQ-788 [10–6-10–16 M]. Migration depth was quantified microscopically. For evaluating histamine release cells were incubated with ET-1 [10–6-10–12 M] for 30min before gaining the supernatants. Additionally, histamine release upon ET-1 stimulation [10–6-10–12 M] was evoked by the secretagogue fMLP [10–5 M]. To show, whether basophils express ETAR or ETBR, RT-PCR was performed, for which human umbilical vein endothelial cells (HUVEC) and peripheral mononuclear cells (PMC) served as controls.

ET-1 [10–6-10–8 M] induced the most significant migratory response (p<0.0001). The ETAR antagonist BQ-123 [10–6-10–12 M] significantly blocked migration towards ET-1 [10–8 M], whereas the ETBR antagonist BQ-788 had no effect. Histamine release was increased by 2.46 to 2.6 fold after ET-1 stimulation [10–6-10–12 M]. Interestingly, only the evoking of histamine release by further stimulation with fMLP [10–5 M] resulted in a dose dependent effect of ET-1, showing ET-1 [10–8 M] being most effective. Furthermore, the RT-PCR proved basophils to express both, ETAR and ETBR.

Our observations reveal for the first time that basophils express both ET-1 receptor types and that ET-1 induces histamine release and the migration of basophils, which seems ETAR dependent. Considering the fact that ET-1 is involved in the mechanisms of airway inflammation, targeting the effects of ET-1 by ET receptor antagonists may be a new option in the treatment of allergic airway disease.