Staphylococcus aureus alpha-toxin attack on human platelets promotes assembly of the prothrombinase complex.
alpha-Toxin, the major cytolysin of Staphylococcus aureus, promotes blood coagulation by its attack on human platelets (Bhakdi S., Muhly, M., Mannhardt, U., Hugo, F., Klapettek, K., Mueller-Eckhardt, C., and Roka, L. (1988) J. Exp. Med. 168, 527-542). In the present study we demonstrate that toxin attack on gel-filtered human platelets initiates the assembly of prothrombinase complexes at rates up to 10-fold of controls. Treatment of platelets with 0.1 microgram/ml alpha-toxin resulted in generation of 1.4 units of thrombin/10(8) platelets. A similar rate of thrombin generation was noted when platelets were subjected to three cycles of freezing and thawing. However, the alpha-toxin-induced prothrombinase activity was not due to platelet lysis, since less than 1% of total cellular lactate dehydrogenase was released by this alpha-toxin concentration. Two distinct and dissociable processes contributed to enhanced prothrombinase assembly. First, alpha-toxin promoted the exocytotic release of factor V from alpha-granules, which was accompanied by co-secretion of platelet factor 4. This process was calcium-dependent. Second, toxin-treated platelets exhibited an enhanced capacity to bind external factor V(a), a phenomenon that was not linked to Ca2(+)-dependent factor V secretion. Assembly of prothrombinase complexes via these two mechanisms together accounts for the procoagulant action of S. aureus alpha-toxin.
Arvand
M
M
Institute of Medical Microbiology, University of Mainz, Federal Republic of Germany.
Bhakdi
S
S
Dahlbäck
B
B
Preissner
K T
KT
D001241:Aspirin / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005165:Factor V / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism*; D015951:Factor Xa; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010978:Platelet Factor 4 / Q000378:metabolism; D012016:Reference Values; D013211:Staphylococcus aureus
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C022475:prothrombinase complex; C021091:staphylococcal alpha-toxin; D010978:Platelet Factor 4; D000001:Calcimycin; D005165:Factor V; D005170:Factor X; D004492:Edetic Acid; D015951:Factor Xa; D001241:Aspirin