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-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.
Teixeira
M M
MM
Applied Pharmacology and Thoracic Medicine, Imperial College of Medicine at the National Heart and Lung Institute, London, UK.
Giembycz
M A
MA
Lindsay
M A
MA
Hellewell
P G
PG
D000818:Animals; D002118:Calcium / Q000502:physiology; D002449:Cell Aggregation / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology*; D037342:Pertussis Toxin; D054799:Phospholipase C beta; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides; D010738:Type C Phospholipases / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D007546:Isoquinolines; D010972:Platelet Activating Factor; D013449:Sulfonamides; D010566:Virulence Factors, Bordetella; D007975:Leukotriene B4; D015936:Complement C5a; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium; C064758:Ro 31-8220