Suppression of platelet aggregation by Bordetella pertussis adenylate cyclase toxin

The effect of Bordetella pertussis adenylate cyclase toxin (ACT) on platele t aggregation was investigated. This cell-invasive adenylate cyclase comple tely suppressed ADP (10 mu M)-induced aggregation of rabbit platelets at 3 mu g/ml and strongly suppressed thrombin (0.2 U/ml)-induced aggregation at 10 mu g/ml. The suppression was accompanied by marked increase in platelet intracellular cyclic AMP (cAMP) content and was diminished by the anti-ACT monoclonal antibody B7E11. A catalytically inactive point mutant of ACT did not show the suppressive effect. Since an increase of cAMP content is a kn own cause of platelet dysfunction, these results indicate that the observed platelet inactivation was due to the catalytic activity of ACT through inc rease of intracellular cAMP.