Pertussis toxin shows distinct early signalling events in platelet- activating factor-, leukotriene B₄-, and C5a-induced eosinophil homotypic aggregation in vitro and recruitment in vivo

The present study was performed to investigate the early signalling events responsible for eosinophil activation in response to platelet- activating factor (PAF), C5a, and leukotriene B₄ (LTB₄). We evaluated the effect of pertussis toxin (PTX) on eosinophil aggregation in vitro and cutaneous eosinophil recruitment in vivo. Further studies using the protein kinase inhibitors Ro 31-8220 and staurosporine were performed in vitro to assess in more detail the early signalling events induced by these three mediators. Our results show that C5a and LTB₄ signal predominantly or exclusively through a PTX-sensitive G protein that is negatively modulated by protein kinase C, possibly at the level of phospholipase C-β. In contrast, PAF activates eosinophils independent of Gi by a mechanism that is abolished by Ro 31-8220, a selective protein kinase C inhibitor. In addition, these results show for the first time that a receptor-operated event on the eosinophil is essential for chemoattractant-induced eosinophil recruitment in vivo.