Signal transduction in human platelets and inflammatory mediator release induced by genetically cloned hemolysin-positive and -negative Escherichia coli strains.
Incubation of human platelets with the hemolysin-producing Escherichia coli strain K-12 (pANN5211) induced the activation of protein kinase C, aggregation of platelets, calcium influx, low amounts of 12-hydroxyeicosatetraenoic acid (12-HETE), and release of serotonin from dense granules. Nonhemolytic isogenic strains of E. coli 536/21 which differed only in their types of adhesins (MSH+ MS-Fim+; S-MRH+ S-Fim+; P-MRH+ P-Fim+) released neither serotonin nor 12-HETE from human platelets nor induced platelet aggregation. All hemolysin-negative bacteria except E. coli 536/21, without any adhesins, were able to activate protein kinase C reversibly but did not induce calcium influx. Activation of platelets with fluoride, an activator of the GTP-binding protein, was associated with protein kinase C activation, calcium influx, platelet aggregation, serotonin release, and 12-HETE formation. The simultaneous stimulation of platelets with NaF and the nonhemolytic E. coli strains suppressed several of the NaF-induced platelet responses. Membrane preparations isolated from stimulated platelets with hemolysin-negative and hemolysin-positive E. coli showed increased binding of guanylylimidodiphosphate, a nonhydrolyzable GTP analog, and enhanced GTPase activity.
König
B
B
Lehrstuhl für Medizinische Mikrobiologie und Immunologie, Arbeitsgruppe für Infektabwehrmechanismen, Ruhr-Universität Bochum, Federal Republic of Germany.
Schönfeld
W
W
Scheffer
J
J
König
W
W
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006460:Hemolysin Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D015539:Platelet Activation; D010974:Platelet Aggregation; D011493:Protein Kinase C / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000494:pharmacology
D018830:Adhesins, Escherichia coli; D001425:Bacterial Outer Membrane Proteins; D006460:Hemolysin Proteins; D006893:Hydroxyeicosatetraenoic Acids; D012701:Serotonin; D006165:Guanylyl Imidodiphosphate; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D012969:Sodium Fluoride; D011493:Protein Kinase C; D020558:GTP Phosphohydrolases; D002118:Calcium