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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
MM Teixeira, MA Giembycz, MA Lindsay and PG Hellewell
Applied Pharmacology and Thoracic Medicine, Imperial College of Medicine at
the National Heart and Lung Institute, London, UK.
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-beta. 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.
Volume 89,
Issue 12,
pp. 4566-4573,
06/15/1997
Copyright © 1997 by The American Society of Hematology
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