Suppression of platelet aggregation by Bordetella pertussis adenylate cyclase toxin.
The effect of Bordetella pertussis adenylate cyclase toxin (ACT) on platelet aggregation was investigated. This cell-invasive adenylate cyclase completely suppressed ADP (10 microM)-induced aggregation of rabbit platelets at 3 micrograms/ml and strongly suppressed thrombin (0. 2 U/ml)-induced aggregation at 10 micrograms/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 known cause of platelet dysfunction, these results indicate that the observed platelet inactivation was due to the catalytic activity of ACT through increase of intracellular cAMP.
Iwaki
M
M
Department of Bacterial and Blood Products, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo 208-0011, Japan. miwaki@nih.go.jp
Kamachi
K
K
Heveker
N
N
Konda
T
T
D000244:Adenosine Diphosphate / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001760:Bleeding Time; D001886:Bordetella pertussis / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D051379:Mice; D037342:Pertussis Toxin; D010974:Platelet Aggregation; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000378:metabolism / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D013917:Thrombin; D000262:Adenylyl Cyclases