Damaging effects of Clostridium perfringens delta toxin on blood platelets and their relevance to ganglioside GM2.
The lytic effect of Clostridium perfringens delta toxin was investigated on goat, human, rabbit, and guinea pig platelets. In contrast to erythrocytes from the latter three species, which are insensitive to the toxin, the platelets were equally lysed by the same amount of toxin. These results suggest the presence of GM2 or GM2-like ganglioside(s) as a specific recognition site of the toxin on platelet plasmic membrane as previously established for sensitive erythrocytes. Plasmic membrane damage of human platelets was evidenced by the release of entrapped alpha-[14C]aminoisobutyric acid used as a cytoplasmic marker. The specific binding of hemolytically active 125I-delta toxin by human and rabbit platelets was practically identical, dose dependent, and inhibitable by GM2. Labeled toxin was also bound by various subcellular organelles separated from rabbit platelets except the 5-hydroxytryptamine (5-HT)-containing dense bodies, suggesting the absence or inaccessibility of GM2 on the surface of the latter organelles. This result correlates with the low amounts of 5-[3H]HT liberated after platelet challenge with delta toxin whereas this mediator was massively liberated upon lysis by the sulfhydryl-activated toxin alveolysin. The levels of M and P forms of phenol sulfotransferase (PST), involved in 5-HT catabolism, were determined in human platelet lysates after challenge with delta toxin, alveolysin, and other disruptive treatments. The low PST-M activities detected after lysis by delta toxin suggest that this isoenzyme is very likely associated to dense bodies in contrast to PST-P which is cytoplasmic. Platelet lysis by the toxin allows easy separation of these organelles.
Jolivet-Reynaud
C
C
Unité des Antigènes Bactériens (UA CNRS 557), Institut Pasteur, Paris, France.
Launay
J M
JM
Alouf
J E
JE
D000621:Aminoisobutyric Acids / Q000097:blood; D000818:Animals; D015239:Arylsulfotransferase; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D005678:G(M2) Ganglioside / Q000097:blood*; D005732:Gangliosides / Q000097:blood*; D006041:Goats; D006168:Guinea Pigs; D006460:Hemolysin Proteins / Q000494:pharmacology; D006801:Humans; D009930:Organic Chemicals; D012701:Serotonin / Q000097:blood; D013301:Streptolysins / Q000494:pharmacology; D013466:Sulfurtransferases / Q000097:blood
D000621:Aminoisobutyric Acids; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C029352:Clostridium perfringens delta-toxin; D005732:Gangliosides; D006460:Hemolysin Proteins; D009930:Organic Chemicals; D013301:Streptolysins; C025964:streptolysin O; D005678:G(M2) Ganglioside; C100049:2-aminoisobutyric acid; D012701:Serotonin; C014963:alveolysin; D013466:Sulfurtransferases; D015239:Arylsulfotransferase